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Rahman M, Akter K, Ahmed KR, Fahim MMH, Aktary N, Park MN, Shin SW, Kim B. Synergistic Strategies for Castration-Resistant Prostate Cancer: Targeting AR-V7, Exploring Natural Compounds, and Optimizing FDA-Approved Therapies. Cancers (Basel) 2024; 16:2777. [PMID: 39199550 PMCID: PMC11352813 DOI: 10.3390/cancers16162777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 07/29/2024] [Accepted: 08/03/2024] [Indexed: 09/01/2024] Open
Abstract
Castration-resistant prostate cancer (CRPC) remains a significant therapeutic challenge due to its resistance to standard androgen deprivation therapy (ADT). The emergence of androgen receptor splice variant 7 (AR-V7) has been implicated in CRPC progression, contributing to treatment resistance. Current treatments, including first-generation chemotherapy, androgen receptor blockers, radiation therapy, immune therapy, and PARP inhibitors, often come with substantial side effects and limited efficacy. Natural compounds, particularly those derived from herbal medicine, have garnered increasing interest as adjunctive therapeutic agents against CRPC. This review explores the role of AR-V7 in CRPC and highlights the promising benefits of natural compounds as complementary treatments to conventional drugs in reducing CRPC and overcoming therapeutic resistance. We delve into the mechanisms of action underlying the anti-CRPC effects of natural compounds, showcasing their potential to enhance therapeutic outcomes while mitigating the side effects associated with conventional therapies. The exploration of natural compounds offers promising avenues for developing novel treatment strategies that enhance therapeutic outcomes and reduce the adverse effects of conventional CRPC therapies. These compounds provide a safer, more effective approach to managing CRPC, representing a significant advancement in improving patient care.
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Affiliation(s)
- Muntajin Rahman
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (M.R.); (K.R.A.); (M.M.H.F.); (N.A.); (M.N.P.)
| | - Khadija Akter
- Department of Plasma Bio Display, Kwangwoon University, Seoul 01897, Republic of Korea;
| | - Kazi Rejvee Ahmed
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (M.R.); (K.R.A.); (M.M.H.F.); (N.A.); (M.N.P.)
| | - Md. Maharub Hossain Fahim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (M.R.); (K.R.A.); (M.M.H.F.); (N.A.); (M.N.P.)
| | - Nahida Aktary
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (M.R.); (K.R.A.); (M.M.H.F.); (N.A.); (M.N.P.)
| | - Moon Nyeo Park
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (M.R.); (K.R.A.); (M.M.H.F.); (N.A.); (M.N.P.)
| | - Sang-Won Shin
- Department of Humanities & Social Medicine, School of Korean Medicine, Pusan National University, 49 Busandaehak-ro, Mulgeum-eup, Yangsan-si 50612, Republic of Korea
| | - Bonglee Kim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (M.R.); (K.R.A.); (M.M.H.F.); (N.A.); (M.N.P.)
- Department of Plasma Bio Display, Kwangwoon University, Seoul 01897, Republic of Korea;
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Auti A, Tathode M, Marino MM, Vitiello A, Ballini A, Miele F, Mazzone V, Ambrosino A, Boccellino M. Nature's weapons: Bioactive compounds as anti-cancer agents. AIMS Public Health 2024; 11:747-772. [PMID: 39416904 PMCID: PMC11474324 DOI: 10.3934/publichealth.2024038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 04/23/2024] [Accepted: 04/28/2024] [Indexed: 10/19/2024] Open
Abstract
Cancer represents a major global health burden, prompting continuous research for effective therapeutic strategies. Natural compounds derived from plants have emerged as potential strategies for preventing cancer and treatment because of their inherent pharmacological properties. This comprehensive review aimed to evaluate the therapeutic potential of five key natural compounds: apigenin, quercetin, piperine, curcumin, and resveratrol in cancer prevention and therapy. By examining their molecular mechanisms and preclinical evidence, this review seeks to elucidate their role as potential adjuvants or stand-alone therapies in cancer management. The exploration of natural compounds as cancer therapeutics offers several advantages, including low toxicity, wide availability, and compatibility with conventional chemotherapeutic agents. We highlighted the current understanding of their anticancer mechanisms and clinical applications for advancing personalized cancer care to improve patient outcomes. We discussed the empirical findings from in vitro, in vivo, and clinical studies reporting biological activity and therapeutic efficacy in antioxidant, immunomodulatory, anti-carcinogenic, and chemo-sensitizing modes. Innovative delivery systems and personalized treatment approaches may further enhance their bioavailability and therapeutic utility in a synergistic approach with chemo- and radiotherapeutic disease management. This review underscores the importance of natural compounds in cancer prevention and treatment, promoting a multidisciplinary approach to the development of innovative therapeutic strategies.
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Affiliation(s)
- Amogh Auti
- Department of Precision Medicine, Università della Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Madhura Tathode
- Department of Precision Medicine, Università della Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Maria Michela Marino
- Department of Precision Medicine, Università della Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Antonio Vitiello
- Ministry of Health, Directorate-General for Health Prevention, 00144 Rome, Italy
| | - Andrea Ballini
- Department of Clinical and Experimental Medicine, University of Foggia, Via Rovelli 50, 71122, Foggia, Italy
| | - Francesco Miele
- General Surgery Unit, Università degli Studi della Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Valeria Mazzone
- Department of Experimental Medicine, Università della Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Alessia Ambrosino
- Department of Experimental Medicine, Università della Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Mariarosaria Boccellino
- Department of Precision Medicine, Università della Campania “Luigi Vanvitelli”, 80138 Naples, Italy
- Department of Life Sciences, Health and Health Professions, Link Campus University, 00165 Rome, Italy
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Cimmino A, Fasciglione GF, Gioia M, Marini S, Ciaccio C. Multi-Anticancer Activities of Phytoestrogens in Human Osteosarcoma. Int J Mol Sci 2023; 24:13344. [PMID: 37686148 PMCID: PMC10487502 DOI: 10.3390/ijms241713344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 08/19/2023] [Accepted: 08/24/2023] [Indexed: 09/10/2023] Open
Abstract
Phytoestrogens are plant-derived bioactive compounds with estrogen-like properties. Their potential health benefits, especially in cancer prevention and treatment, have been a subject of considerable research in the past decade. Phytoestrogens exert their effects, at least in part, through interactions with estrogen receptors (ERs), mimicking or inhibiting the actions of natural estrogens. Recently, there has been growing interest in exploring the impact of phytoestrogens on osteosarcoma (OS), a type of bone malignancy that primarily affects children and young adults and is currently presenting limited treatment options. Considering the critical role of the estrogen/ERs axis in bone development and growth, the modulation of ERs has emerged as a highly promising approach in the treatment of OS. This review provides an extensive overview of current literature on the effects of phytoestrogens on human OS models. It delves into the multiple mechanisms through which these molecules regulate the cell cycle, apoptosis, and key pathways implicated in the growth and progression of OS, including ER signaling. Moreover, potential interactions between phytoestrogens and conventional chemotherapy agents commonly used in OS treatment will be examined. Understanding the impact of these compounds in OS holds great promise for developing novel therapeutic approaches that can augment current OS treatment modalities.
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Affiliation(s)
| | | | | | | | - Chiara Ciaccio
- Department of Clinical Sciences and Translational Medicine, University of Rome ‘Tor Vergata’, Via Montpellier 1, I-00133 Rome, Italy; (A.C.); (G.F.F.); (M.G.); (S.M.)
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Chen YT, Chen SJ, Hu CY, Dong CD, Chen CW, Singhania RR, Hsieh SL. Exploring the Anti-Cancer Effects of Fish Bone Fermented Using Monascus purpureus: Induction of Apoptosis and Autophagy in Human Colorectal Cancer Cells. Molecules 2023; 28:5679. [PMID: 37570647 PMCID: PMC10419882 DOI: 10.3390/molecules28155679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 07/24/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
Fish bone fermented using Monascus purpureus (FBF) has total phenols and functional amino acids that contribute to its anti-oxidant and anti-inflammatory properties. Colorectal cancer, one of the most prevalent cancers and the third largest cause of death worldwide, has become a serious threat to global health. This study investigates the anti-cancer effects of FBF (1, 2.5 or 5 mg/mL) on the cell growth and molecular mechanism of HCT-116 cells. The HCT-116 cell treatment with 2.5 or 5 mg/mL of FBF for 24 h significantly decreased cell viability (p < 0.05). The S and G2/M phases significantly increased by 88-105% and 25-43%, respectively (p < 0.05). Additionally, FBF increased the mRNA expression of caspase 8 (38-77%), protein expression of caspase 3 (34-94%), poly (ADP-ribose) polymerase (PARP) (31-34%) and induced apoptosis (236-773%) of HCT-116 cells (p < 0.05). FBF also increased microtubule-associated protein 1B light chain 3 (LC3) (38-48%) and phosphoinositide 3 kinase class III (PI3K III) (32-53%) protein expression, thereby inducing autophagy (26-52%) of HCT-116 cells (p < 0.05). These results showed that FBF could inhibit HCT-116 cell growth by inducing S and G2/M phase arrest of the cell cycle, apoptosis and autophagy. Thus, FBF has the potential to treat colorectal cancer.
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Affiliation(s)
- Ya-Ting Chen
- Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung 81157, Taiwan;
| | - Shu-Jen Chen
- Department of Chemical and Materials Engineering, National Kaohsiung University of Science and Technology, Kaohsiung 80778, Taiwan;
| | - Chun-Yi Hu
- Department of Food Science and Nutrition, Meiho University, Pingtung 912009, Taiwan;
| | - Cheng-Di Dong
- Department of Marine Environmental Engineering, National Kaohsiung University of Science and Technology, Kaohsiung 81157, Taiwan; (C.-D.D.); (C.-W.C.); (R.R.S.)
| | - Chiu-Wen Chen
- Department of Marine Environmental Engineering, National Kaohsiung University of Science and Technology, Kaohsiung 81157, Taiwan; (C.-D.D.); (C.-W.C.); (R.R.S.)
| | - Reeta Rani Singhania
- Department of Marine Environmental Engineering, National Kaohsiung University of Science and Technology, Kaohsiung 81157, Taiwan; (C.-D.D.); (C.-W.C.); (R.R.S.)
| | - Shu-Ling Hsieh
- Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung 81157, Taiwan;
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Surien O, Masre SF, Basri DF, Ghazali AR. Potential Chemopreventive Role of Pterostilbene in Its Modulation of the Apoptosis Pathway. Int J Mol Sci 2023; 24:ijms24119707. [PMID: 37298657 DOI: 10.3390/ijms24119707] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 04/08/2023] [Accepted: 04/21/2023] [Indexed: 06/12/2023] Open
Abstract
Cancer incidence keeps increasing every year around the world and is one of the leading causes of death worldwide. Cancer has imposed a major burden on the human population, including the deterioration of physical and mental health as well as economic or financial loss among cancer patients. Conventional cancer treatments including chemotherapy, surgery, and radiotherapy have improved the mortality rate. However, conventional treatments have many challenges; for example, drug resistance, side effects, and cancer recurrence. Chemoprevention is one of the promising interventions to reduce the burden of cancer together with cancer treatments and early detection. Pterostilbene is a natural chemopreventive compound with various pharmacological properties such as anti-oxidant, anti-proliferative, and anti-inflammatory properties. Moreover, pterostilbene, due to its potential chemopreventive effect on inducing apoptosis in eliminating the mutated cells or preventing the progression of premalignant cells to cancerous cells, should be explored as a chemopreventive agent. Hence, in the review, we discuss the role of pterostilbene as a chemopreventive agent against various types of cancer via its modulation of the apoptosis pathway at the molecular levels.
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Affiliation(s)
- Omchit Surien
- Center for Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Kuala Lumpur 50300, Malaysia
| | - Siti Fathiah Masre
- Center for Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Kuala Lumpur 50300, Malaysia
| | - Dayang Fredalina Basri
- Center for Diagnostic, Therapeutic & Investigative Studies (CODTIS), Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Kuala Lumpur 50300, Malaysia
| | - Ahmad Rohi Ghazali
- Center for Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Kuala Lumpur 50300, Malaysia
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Curcumin Release from Biomaterials for Enhanced Tissue Regeneration Following Injury or Disease. Bioengineering (Basel) 2023; 10:bioengineering10020262. [PMID: 36829756 PMCID: PMC9951943 DOI: 10.3390/bioengineering10020262] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 02/12/2023] [Accepted: 02/14/2023] [Indexed: 02/18/2023] Open
Abstract
Curcumin, a bioactive phenol derived from turmeric, is an antioxidant, anti-inflammatory, and antibacterial molecule. Although curcumin exhibits beneficial effects in its innate form, it is highly hydrophobic, which leads to poor water solubility and, consequently, low bioavailability. The lack of bioavailability limits curcumin's effectiveness as a treatment and restricts its use in clinical applications. Furthermore, to achieve beneficial, clinically relevant results, high doses of curcumin are required for systemic administration. Many researchers have utilized biomaterial carriers, including electrospun fibers, nanoparticles, hydrogels, and composite scaffolds, to overcome curcumin's principle therapeutic limitation of low bioavailability. By using biomaterials to deliver curcumin directly to injury sites, researchers have harnessed the beneficial natural properties of curcumin while providing scaffolding to support tissue regeneration. This review will provide an in-depth overview of the literature that utilizes biomaterial delivery of curcumin for tissue regeneration in injury and disease models.
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Kah G, Chandran R, Abrahamse H. Curcumin a Natural Phenol and Its Therapeutic Role in Cancer and Photodynamic Therapy: A Review. Pharmaceutics 2023; 15:pharmaceutics15020639. [PMID: 36839961 PMCID: PMC9962422 DOI: 10.3390/pharmaceutics15020639] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 02/07/2023] [Accepted: 02/10/2023] [Indexed: 02/16/2023] Open
Abstract
Cancer continues to cause an alarming number of deaths globally, and its burden on the health system is significant. Though different conventional therapeutic procedures are exploited for cancer treatment, the prevalence and death rates remain elevated. These, therefore, insinuate that novel and more efficient treatment procedures are needed for cancer. Curcumin, a bioactive, natural, phenolic compound isolated from the rhizome of the herbaceous plant turmeric, is receiving great interest for its exciting and broad pharmacological properties. Curcumin presents anticancer therapeutic capacities and can be utilized as a photosensitizing drug in cancer photodynamic therapy (PDT). Nonetheless, curcumin's poor bioavailability and related pharmacokinetics limit its clinical utility in cancer treatment. This review looks at the physical and chemical properties, bioavailability, and safety of curcumin, while focusing on curcumin as an agent in cancer therapy and as a photosensitizer in cancer PDT. The possible mechanisms and cellular targets of curcumin in cancer therapy and PDT are highlighted. Furthermore, recent improvements in curcumin's bioavailability in cancer therapy using nanoformulations and delivery systems are presented.
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Gadi V, Shetty SR. Potential of Anti-inflammatory Molecules in the Chemoprevention of Breast Cancer. RECENT ADVANCES IN INFLAMMATION & ALLERGY DRUG DISCOVERY 2022; 16:60-76. [PMID: 36043708 DOI: 10.2174/2772270816666220829090716] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 06/23/2022] [Accepted: 06/27/2022] [Indexed: 01/20/2023]
Abstract
Breast cancer is a global issue, affecting greater than 1 million women per annum. Over the past two decades, there have been numerous clinical trials involving the use of various pharmacological substances as chemopreventive agents for breast cancer. Various pre-clinical as well as clinical studies have established numerous anti-inflammatory molecules, including nonsteroidal anti-inflammatory drugs (NSAIDs) and dietary phytochemicals as promising agents for chemoprevention of several cancers, including breast cancer. The overexpression of COX-2 has been detected in approximately 40% of human breast cancer cases and pre-invasive ductal carcinoma in-situ lesions, associated with aggressive elements of breast cancer such as large size of the tumour, ER/PR negative and HER-2 overexpression, among others. Anti-inflammatory molecules inhibit COX, thereby inhibiting the formation of prostaglandins and inhibiting nuclear factor-κBmediated signals (NF-kB). Another probable explanation entails inflammation-induced degranulation, with the production of angiogenesis-regulating factors, such as vascular endothelial growth factor, which can be possibly regulated by anti-inflammatory molecules. Apart from NSAIDS, many dietary phytochemicals have the ability to decrease, delay, or stop the progression and/or incidence of breast cancer by their antioxidant action, regulating inflammatory and proliferative cell signalling pathways as well as inducing apoptosis. The rapid progress in chemoprevention research has also established innovative strategies that can be implemented to prevent breast cancer. This article gives a comprehensive overview of the recent advancements in using antiinflammatory molecules in the chemoprevention of breast cancer along with their mechanism of action, supported by latest preclinical and clinical data. The merits of anti-inflammatory chemopreventive agents in the prevention of cardiotoxicity have been described. We have also highlighted the ongoing research and advancements in improving the efficacy of using antiinflammatory molecules as chemopreventive agents.
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Affiliation(s)
- Vaishnavi Gadi
- Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKMS Narsee Monjee Institute of Management Studies, Mumbai-56, Maharashtra, India
| | - Saritha Rakesh Shetty
- Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKMS Narsee Monjee Institute of Management Studies, Mumbai-56, Maharashtra, India
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Recent Overview of Resveratrol's Beneficial Effects and Its Nano-Delivery Systems. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27165154. [PMID: 36014390 PMCID: PMC9414442 DOI: 10.3390/molecules27165154] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 08/09/2022] [Accepted: 08/10/2022] [Indexed: 11/17/2022]
Abstract
Highlights Abstract Natural polyphenols have a wide variety of biological activities and are taken into account as healthcare materials. Resveratrol is one such natural polyphenol, belonging to a group known as stilbenoids (STBs). Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is mainly found in grapes, wine, nuts, and berries. A wide range of biological activities has been demonstrated by resveratrol, including antimicrobial, antioxidant, antiviral, antifungal, and antiaging effects, and many more are still under research. However, as with many other plant-based polyphenol products, resveratrol suffers from low bioavailability once administered in vivo due to its susceptibility to rapid enzyme degradation by the body’s innate immune system before it can exercise its therapeutic influence. Therefore, it is of the utmost importance to ensure the best use of resveratrol by creating a proper resveratrol delivery system. Nanomedicine and nanodelivery systems utilize nanoscale materials as diagnostic tools or to deliver therapeutic agents in a controlled manner to specifically targeted locations. After a brief introduction about polyphenols, this review overviews the physicochemical characteristics of resveratrol, its beneficial effects, and recent advances on novel nanotechnological approaches for its delivery according to the type of nanocarrier utilized. Furthermore, the article summarizes the different potential applications of resveratrol as, for example, a therapeutic and disease-preventing anticancer and antiviral agent.
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Fuloria S, Mehta J, Chandel A, Sekar M, Rani NNIM, Begum MY, Subramaniyan V, Chidambaram K, Thangavelu L, Nordin R, Wu YS, Sathasivam KV, Lum PT, Meenakshi DU, Kumarasamy V, Azad AK, Fuloria NK. A Comprehensive Review on the Therapeutic Potential of Curcuma longa Linn. in Relation to its Major Active Constituent Curcumin. Front Pharmacol 2022; 13:820806. [PMID: 35401176 PMCID: PMC8990857 DOI: 10.3389/fphar.2022.820806] [Citation(s) in RCA: 111] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 01/27/2022] [Indexed: 12/16/2022] Open
Abstract
Curcuma longa Linn. (C. longa), popularly known as turmeric, belongs to the Zingiberaceae family and has a long historical background of having healing properties against many diseases. In Unani and Ayurveda medicine, C. longa has been used for liver obstruction and jaundice, and has been applied externally for ulcers and inflammation. Additionally, it is employed in several other ailments such as cough, cold, dental issues, indigestion, skin infections, blood purification, asthma, piles, bronchitis, tumor, wounds, and hepatic disorders, and is used as an antiseptic. Curcumin, a major constituent of C. longa, is well known for its therapeutic potential in numerous disorders. However, there is a lack of literature on the therapeutic potential of C. longa in contrast to curcumin. Hence, the present review aimed to provide in-depth information by highlighting knowledge gaps in traditional and scientific evidence about C. longa in relation to curcumin. The relationship to one another in terms of biological action includes their antioxidant, anti-inflammatory, neuroprotective, anticancer, hepatoprotective, cardioprotective, immunomodulatory, antifertility, antimicrobial, antiallergic, antidermatophytic, and antidepressant properties. Furthermore, in-depth discussion of C. longa on its taxonomic categorization, traditional uses, botanical description, phytochemical ingredients, pharmacology, toxicity, and safety aspects in relation to its major compound curcumin is needed to explore the trends and perspectives for future research. Considering all of the promising evidence to date, there is still a lack of supportive evidence especially from clinical trials on the adjunct use of C. longa and curcumin. This prompts further preclinical and clinical investigations on curcumin.
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Affiliation(s)
| | - Jyoti Mehta
- Faculty of Applied Sciences and Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan, India
| | - Aditi Chandel
- Faculty of Applied Sciences and Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan, India
| | - Mahendran Sekar
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Malaysia
| | - Nur Najihah Izzati Mat Rani
- Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Malaysia
| | - M. Yasmin Begum
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | | | - Kumarappan Chidambaram
- Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | - Lakshmi Thangavelu
- Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
| | - Rusli Nordin
- Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor, Malaysia
| | - Yuan Seng Wu
- Department of Biological Sciences and Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Selangor, Malaysia
| | | | - Pei Teng Lum
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Malaysia
| | | | - Vinoth Kumarasamy
- Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor, Malaysia
- Department of Preclinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Perak, Malaysia
| | | | - Neeraj Kumar Fuloria
- Faculty of Pharmacy, AIMST University, Kedah, Malaysia
- Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
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Jang JH, Park CY, Sung EG, Song IH, Kim JY, Jung C, Sohn HY, Lee TJ. Lactucin induces apoptosis through reactive oxygen species-mediated BCL-2 and CFLAR L downregulation in Caki-1 cells. Genes Genomics 2021; 43:1199-1207. [PMID: 34302634 DOI: 10.1007/s13258-021-01142-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 07/18/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND Lactucin, a naturally occurring active sesquiterpene lactone, is abundantly found in chicory and romaine lettuce. A recent study reported that lactucin could induce apoptosis in leukemia cells. However, its cytotoxicity and potential molecular mechanisms underlying cancer cell death remain unclear. OBJECTIVE Therefore, in this study, we aimed to investigate the direct effect and underlying mechanism of action of lactucin on renal cancer cells. METHODS MTT assay and flow cytometry were performed to evaluate the rate of cell proliferation and apoptosis, respectively. Western blotting, reverse transcription polymerase chain reaction, and protein stability analyses were performed to analyze the effect of lactucin on the expression of apoptosis-related proteins such as B-cell lymphoma 2 (BCL-2) and CFLAR (CASP8 and FADD like apoptosis regulator) long isoform (CFLARL) in Caki-1 human renal cancer cells. In addition, reactive oxygen species (ROS) generation was evaluated using flow cytometry. RESULTS Lactucin treatment induced apoptosis in Caki-1 cells in a dose-dependent manner via activation of the caspase pathway. It downregulated BCL-2 and CFLARL expression levels by suppressing BCL-2 transcription and CFLARL protein stability, respectively. Pretreatment with N-acetyl-1-cysteine, a ROS scavenger, attenuated the lactucin-induced apoptosis and restored the BCL-2 and CFLARL expression to basal levels. Lactucin-facilitated BCL-2 downregulation was regulated at the transcriptional level through the inactivation of the NF-κB pathway. CONCLUSIONS Our study is the first to demonstrate that lactucin-induced apoptosis is mediated by ROS production, which in turn activates the caspase-dependent apoptotic pathway by inhibiting BCL-2 and CFLARL expression in Caki-1 cells.
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Affiliation(s)
- Ji Hoon Jang
- Department of Anatomy, College of Medicine, Yeungnam University, 170 Hyeonchung-ro, Nam-Gu, 42415, Daegu, South Korea
| | - Cho-Young Park
- Department of Anatomy, College of Medicine, Yeungnam University, 170 Hyeonchung-ro, Nam-Gu, 42415, Daegu, South Korea
| | - Eon-Gi Sung
- Department of Anatomy, College of Medicine, Yeungnam University, 170 Hyeonchung-ro, Nam-Gu, 42415, Daegu, South Korea
| | - In-Hwan Song
- Department of Anatomy, College of Medicine, Yeungnam University, 170 Hyeonchung-ro, Nam-Gu, 42415, Daegu, South Korea
| | - Joo-Young Kim
- Department of Anatomy, College of Medicine, Yeungnam University, 170 Hyeonchung-ro, Nam-Gu, 42415, Daegu, South Korea
| | - Chuleui Jung
- Department of Plant Medicals, Andong National University, 36729, Andong, South Korea
| | - Ho-Yong Sohn
- Department of Food and Nutrition, Andong National University, 36729, Andong, South Korea.
| | - Tae-Jin Lee
- Department of Anatomy, College of Medicine, Yeungnam University, 170 Hyeonchung-ro, Nam-Gu, 42415, Daegu, South Korea.
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Shetty NP, Prabhakaran M, Srivastava AK. Pleiotropic nature of curcumin in targeting multiple apoptotic-mediated factors and related strategies to treat gastric cancer: A review. Phytother Res 2021; 35:5397-5416. [PMID: 34028111 DOI: 10.1002/ptr.7158] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 04/21/2021] [Accepted: 04/30/2021] [Indexed: 12/24/2022]
Abstract
Gastric cancer (GC) is one of the major reasons for cancer-associated death and exhibits the second-highest mortality rate worldwide. Several advanced approaches have been designed to treat GC; however, these strategies possess many innate complications. In view of this, the upcoming research relying on natural products could result in designing potential anticancer agents with fewer side effects. Curcumin, isolated from the rhizomes of Curcuma longa L. has several medicinal properties like antiinflammatory, antioxidant, antiapoptotic, antitumor, and antimetastatic. Such pleiotropic nature of curcumin impedes the invasion and proliferation of GC by targeting several oncogenic factors like p23, human epidermal factor receptor2 including Helicobacter pylori. The side effect of chemotherapy, that is, chemotherapeutic resistance and radiotherapy could be reduced combination therapy of curcumin. Moreover, the photodynamic therapy of curcumin destroys the cancer cells without affecting normal cells. However, further more potential studies are required to establish the potent efficacy of curcumin in the treatment of GC. The current review details the anticancer activities of curcumin and related strategies which could be employed to treat GC with additional focus on its inhibitory properties against viability, proliferation, and migration of GC cells through cell cycle arrest and stimulation by apoptosis-mediated factors.
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Affiliation(s)
- Nandini P Shetty
- Plant Cell Biotechnology Department, CSIR-Central Food Technological Research Institute, Mysore, 570020, India
| | - Manoj Prabhakaran
- Plant Cell Biotechnology Department, CSIR-Central Food Technological Research Institute, Mysore, 570020, India
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13
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Antibacterial Activity of Rosmarinus officinalis against Multidrug-Resistant Clinical Isolates and Meat-Borne Pathogens. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:6677420. [PMID: 34007297 PMCID: PMC8102098 DOI: 10.1155/2021/6677420] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 03/19/2021] [Accepted: 04/16/2021] [Indexed: 01/07/2023]
Abstract
Background In developing countries, the prevalence of bacterial infections is quite rampant due to several factors such as the HIV/AIDS pandemic, lack of hygiene, overcrowding, and resistance to conventional antimicrobials. Hence the use of plant-based antimicrobial agents could provide a low-cost alternative therapy. Rosmarinus officinalis is reputed as a medicinal plant in Ethiopia; however, its antibacterial activity against many of the clinical isolates remains overlooked. Methods Tender foliage of R. officinalis was collected and extracted in ethanol (EtOH) and evaluated for their antimicrobial activity against ten multidrug-resistant (MDR) clinical isolates, human type culture pathogens, and meat-borne bacterial isolates by employing agar well diffusion assay. Results EtOH extract of R. officinalis efficiently subdued the growth of all tested MDR clinical isolates in varying degrees. Salmonella sp. and Staphylococcus aureus were found to be the most sensitive clinical isolates. Likewise, it efficiently repressed the growth of meat-borne pathogens, particularly, S. aureus and Salmonella sp. showing its potentiality to be used as a natural antibacterial agent in the meat processing industry. The mechanism of antibiosis of plant extract against meat-borne pathogens is inferred to be bactericidal. Chemical constituents of the crude plant extract were analysed by Gas Chromatography-Mass Spectroscopy (GC-MS), Fourier Transform Infrared (FT-IR), and UV-visible spectroscopy showing genkwanin (26%), camphor (13%), endo-borneol (13%), alpha-terpineol (12%), and hydroxyhydrocaffeic acid (13%) as the major compounds. Conclusion Overall results of the present study conclude that R. officinalis could be an excellent source of antimicrobial agents for the management of drug-resistant bacteria as well as meat-borne pathogens.
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Sarvizadeh M, Hasanpour O, Naderi Ghale-Noie Z, Mollazadeh S, Rezaei M, Pourghadamyari H, Masoud Khooy M, Aschner M, Khan H, Rezaei N, Shojaie L, Mirzaei H. Allicin and Digestive System Cancers: From Chemical Structure to Its Therapeutic Opportunities. Front Oncol 2021; 11:650256. [PMID: 33987085 PMCID: PMC8111078 DOI: 10.3389/fonc.2021.650256] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 02/10/2021] [Indexed: 12/24/2022] Open
Abstract
Digestive system cancer tumors are one of the major causes of cancer-related fatalities; the vast majority of them are colorectal or gastric malignancies. Epidemiological evidence confirmed that allium-containing food, such as garlic, reduces the risk of developing malignancies. Among all compounds in garlic, allicin has been most researched, as it contains sulfur and produces many second degradation compounds, such as sulfur dioxide, diallyl sulfide (DAS), diallyl trisulfide (DATS), and diallyl disulfide (DADS) in the presence of enzymatic reactions in gastric juice. These substances have shown anti-inflammatory, antidiabetic, antihypertensive, antifungal, antiviral, antibacterial, and anticancer efficacy, including gastrointestinal (GI) cancers, leukemia, and skin cancers. Herein, we summarize the therapeutic potential of allicin in the treatment of GI cancers.
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Affiliation(s)
- Mahshad Sarvizadeh
- Nutrition and Endocrine Research Centre, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Omid Hasanpour
- School of Paramedicine, Kashan University of Medical Sciences, Kashan, Iran
| | | | - Samaneh Mollazadeh
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Mohammad Rezaei
- Department of Diabetes, Obesity and Metabolism, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Hossein Pourghadamyari
- Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan
| | - Nima Rezaei
- Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Layla Shojaie
- Department of Medicine, Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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Harikrishnan A, Khanna S, Veena V. Design of New Improved Curcumin Derivatives to Multi-targets of Cancer and Inflammation. Curr Drug Targets 2021; 22:573-589. [PMID: 32753008 DOI: 10.2174/1389450121666200804113745] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 05/11/2020] [Accepted: 05/11/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Curcumin is a major active principle of Curcuma longa. There are more than 1700 citations in the Medline, reflecting various biological effects of curcumin. Most of these biological activities are associated with the antioxidant, anti-inflammatory and antitumor activity of the molecule. Several reports suggest various targets of natural curcumin that include growth factors, growth factor receptor, cytokines, enzymes and gene regulators of apoptosis. This review focuses on the improved curcumin derivatives that target the cancer and inflammation. METHODOLOGY In this present review, we explored the anticancer drugs with curcumin-based drugs under pre-clinical and clinical studies with critical examination. Based on the strong scientific reports of patentable and non-patented literature survey, we have investigated the mode of the interactions of curcumin-based molecules with the target molecules. RESULTS Advanced studies have added new dimensions of the molecular response of cancer cells to curcumin at the genomic level. However, poor bioavailability of the molecule seems to be the major limitation of the curcumin. Several researchers have been involved to improve the curcumin derivatives to overcome this limitation. Sufficient data of clinical trials to various cancers that include multiple myeloma, pancreatic cancer and colon cancer, have also been discussed. CONCLUSION The detailed analysis of the structure-activity relationship (SAR) and common synthesis of curcumin-based derivatives have been discussed in the review. Utilising the predictions of in silico coupled with validation reports of in vitro and in vivo studies have concluded many targets for curcumin. Among them, cancer-related inflammation genes regulating curcumin-based molecules are a very promising target to overcome hurdles in the multimodality therapy of cancer.
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Affiliation(s)
- A Harikrishnan
- Department of Chemistry, School of Arts and Sciences, Vinayaka Mission Research Foundation-Aarupadai Veedu (VMRF-AV) campus, Paiyanoor, Chennai-603104, Tamil Nadu, India
| | - Sunali Khanna
- Nair Hospital Dental College, Municipal Corporation of Greater Mumbai, Mumbai, 400 008, India
| | - V Veena
- Department of Biotechnology, School of Applied Sciences, REVA University, Rukmini knowledge park, Kattigenahalli, Yelahanka, Bengaluru - 5600 064. Karnataka State, India
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Liu Z, Smart JD, Pannala AS. Recent developments in formulation design for improving oral bioavailability of curcumin: A review. J Drug Deliv Sci Technol 2020. [DOI: 10.1016/j.jddst.2020.102082] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Effects of dietary curcumin on growth, antioxidant capacity, fatty acid composition and expression of lipid metabolism-related genes of large yellow croaker fed a high-fat diet. Br J Nutr 2020; 126:345-354. [PMID: 33076999 DOI: 10.1017/s0007114520004171] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
A 10-week feeding trial was conducted to investigate the effect of dietary curcumin (CC) on growth antioxidant responses, fatty acid composition, and expression of lipid metabolism-related genes of large yellow croaker fed a high-fat diet (HFD). Four diets (lipid level at 18 %) were formulated with different levels of curcumin (0, 0·02, 0·04 and 0·06 %). The best growth performance was found in the 0·04 % curcumin group, with the body and hepatic lipid levels lower than the control group (0 % CC). The content of TAG, total cholesterol and LDL-cholesterol was the least in the 0·06 % curcumin group. The lowest malondialdehyde and the highest superoxide dismutase, catalase and total antioxidant capacity were observed in the 0·04 % curcumin group. The 0·04 % curcumin group had higher expression of Δ6fad, elovl5 and elovl4 and showed higher hepatic n-6 and n-3 PUFA. Expression of ppara, cpt1, and aco was significantly increased, while expression of srebp1 and fas was dramatically decreased in curcumin groups compared with the control group. Overall, 0·04 % curcumin supplementation could mitigate the negative effects caused by HFD and promote growth via reducing hepatic lipid deposition, improving antioxidant activity and increasing PUFA of large yellow croaker. To conclude, abnormal hepatic lipid deposition was probably due to increased fatty acid oxidation and reduced de novo synthesis of fatty acids.
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18
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Lim WF, Mohamad Yusof MI, Teh LK, Salleh MZ. Significant Decreased Expressions of CaN, VEGF, SLC39A6 and SFRP1 in MDA-MB-231 Xenograft Breast Tumor Mice Treated with Moringa oleifera Leaves and Seed Residue (MOLSr) Extracts. Nutrients 2020; 12:nu12102993. [PMID: 33007803 PMCID: PMC7601446 DOI: 10.3390/nu12102993] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 09/17/2020] [Accepted: 09/18/2020] [Indexed: 11/18/2022] Open
Abstract
Moringa oleifera is a miracle plant with many nutritional and medicinal properties. Chemopreventive values of the combined mixture of moringa leaves and seed residue (MOLSr) at different ratios (M1S9, M1S1 and M9S1) were investigated. MOLSr extracts were subjected to phytochemical screening, antioxidant assays, metabolite profiling and cytotoxic activity on the primary mammary epithelial cells (PMECs), non-malignant Chang’s liver cells and various human cancer cell lines (including breast, cervical, colon and liver cancer cell lines). The MOLSr ratio with the most potent cytotoxic activity was used in xenograft mice injected with MDA-MB-231 cells for in vivo tumorigenicity study as well as further protein and gene expression studies. M1S9, specifically composed of saponin and amino acid, retained the lowest antioxidant activity but the highest glucosinolate content as compared to other ratios. Cell viability decreased significantly in MCF-7 breast cancer cells and PMECs after treatment with M1S9. Solid tumor from MDA-MB-231 xenograft mice was inhibited by up to 64.5% at third week after treatment with high-dose M1S9. High-dose M1S9 significantly decreased the expression of calcineurin (CaN) and vascular endothelial cell growth factor (VEGF) proteins as well as the secreted frizzled-related protein 1 (SFRP1) and solute carrier family 39 member 6 (SLC39A6) genes. This study provides new scientific evidence for the chemoprevention potential of MOLSr extracts in a breast cancer model; however, the precise mechanism warrants further investigation.
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Affiliation(s)
- Wai Feng Lim
- Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam 42300, Selangor Darul Ehsan, Malaysia; (W.F.L.); (M.I.M.Y.)
| | - Mohd Izwan Mohamad Yusof
- Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam 42300, Selangor Darul Ehsan, Malaysia; (W.F.L.); (M.I.M.Y.)
| | - Lay Kek Teh
- Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam 42300, Selangor Darul Ehsan, Malaysia; (W.F.L.); (M.I.M.Y.)
- Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam 42300, Selangor Darul Ehsan, Malaysia
- Correspondence: ; (L.K.T.); (M.Z.S.); Tel.: +60-3-3258-4658 (L.K.T. & M.Z.S.)
| | - Mohd Zaki Salleh
- Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam 42300, Selangor Darul Ehsan, Malaysia; (W.F.L.); (M.I.M.Y.)
- Correspondence: ; (L.K.T.); (M.Z.S.); Tel.: +60-3-3258-4658 (L.K.T. & M.Z.S.)
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Xiao W, Liu Y, Dai M, Li Y, Peng R, Yu S, Liu H. Rotenone restrains colon cancer cell viability, motility and epithelial‑mesenchymal transition and tumorigenesis in nude mice via the PI3K/AKT pathway. Int J Mol Med 2020; 46:700-708. [PMID: 32626924 PMCID: PMC7307809 DOI: 10.3892/ijmm.2020.4637] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 03/06/2020] [Indexed: 12/11/2022] Open
Abstract
Rotenone, a natural hydrophobic pesticide, has been reported to display anticancer activity in a variety of cancer cells. However, the mechanism of rotenone on colon cancer (CC) cell migration, invasion and metastasis is still unknown. In the present study, the cytotoxicity of rotenone on CC cells were detected by the Cell Counting Kit‑8 assay and confirmed by clone formation assay. The effects of rotenone on CC cell invasion and migration activity were determined in vitro by Transwell invasion and wound healing assays, respectively. In addition, to reveal whether rotenone affected the epithelial‑mesenchymal‑transition (EMT) process, reverse transcription‑quantitative PCR, western blotting and immunofluorescence assays were used to detect the expression of EMT markers. The expression levels of the key markers of the PI3K/AKT pathway after rotenone treatment alone or in combination with a PI3K/AKT signaling activator in CC were also detected by western blotting. Finally, the in vivo antitumor effects of rotenone were evaluated in a subcutaneous xenotransplant tumor model treated with an intraperitoneal injection of rotenone. The results of the present study demonstrated that rotenone treatment induced CC cell cytotoxicity and greater effects were observed with increasing concentrations and inhibited cell proliferation compared with untreated cells. In vitro cell function assays revealed that rotenone inhibited CC cell migration, invasion and EMT compared with untreated cells. Mechanically, the phosphorylation levels of AKT and mTOR were downregulated in rotenone‑treated CC cells compared with untreated cells. Additionally, AKT and mTOR phosphorylation levels were increased by the PI3K/AKT signaling activator insulin‑like growth factor 1 (IGF‑1), which was reversed by rotenone treatment. The cell function assays confirmed that the IGF‑1‑activated cell proliferation, migration and invasion were decreased by rotenone treatment. These results indicated that rotenone affected CC cell proliferation and metastatic capabilities by inhibiting the PI3K/AKT/mTOR signaling pathway. In addition, rotenone inhibited tumor growth and metastatic capability of CC, which was confirmed in a xenograft mouse model. In conclusion, the present study revealed that rotenone inhibited CC cell viability, motility, EMT and metastasis in vitro and in vivo by inhibiting the PI3K/AKT/mTOR signaling pathway.
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Affiliation(s)
- Wenbo Xiao
- Department of Digestion, University-Town Hospital of Chongqing Medical University, Chongqing 401331
| | | | | | - Yu Li
- Department of Digestion, Rongchang District People's Hospital of Chongqing, Chongqing 402460
| | - Renqun Peng
- Department of Digestion, Rongchang District People's Hospital of Chongqing, Chongqing 402460
| | - Shuangjiang Yu
- Department of Neurosurgery, The First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing 400038, P.R. China
| | - Hao Liu
- Department of Digestion, Rongchang District People's Hospital of Chongqing, Chongqing 402460
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Cost Effective Use of a Thiosulfinate-Enriched Allium sativum Extract in Combination with Chemotherapy in Colon Cancer. Int J Mol Sci 2020; 21:ijms21082766. [PMID: 32316312 PMCID: PMC7216288 DOI: 10.3390/ijms21082766] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Revised: 04/13/2020] [Accepted: 04/14/2020] [Indexed: 02/07/2023] Open
Abstract
In this work, we sought to investigate the effects of a thiosulfinate-enriched garlic extract, co-administered with 5-fluorouracil (5-FU) or oxaliplatin chemotherapy, on the viability of colon cancer cells (Caco-2 and HT-29). We also addressed the economic feasibility of a new combined treatment of this thiosulfinate-enriched garlic extract, with oxaliplatin that could reduce the dosage and costs of a monotherapy. The thiosulfinate-enriched garlic extract not only enhanced the impact of 5-FU and oxaliplatin (500 µM) in decreasing Caco-2 and HT-29 viability, but also showed a higher effect than standard 5-FU and oxaliplatin chemotherapy as anti-cancer agents. These results provided evidences for the combination of lyophilized garlic extract and 5-FU or oxaliplatin as a novel chemotherapy regimen in colon cancer cells that may also reduce the clinical therapy costs.
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21
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Abd. Wahab NA, H. Lajis N, Abas F, Othman I, Naidu R. Mechanism of Anti-Cancer Activity of Curcumin on Androgen-Dependent and Androgen-Independent Prostate Cancer. Nutrients 2020; 12:E679. [PMID: 32131560 PMCID: PMC7146610 DOI: 10.3390/nu12030679] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 02/22/2020] [Accepted: 02/26/2020] [Indexed: 12/22/2022] Open
Abstract
Prostate cancer (PCa) is a heterogeneous disease and ranked as the second leading cause of cancer-related deaths in males worldwide. The global burden of PCa keeps rising regardless of the emerging cutting-edge technologies for treatment and drug designation. There are a number of treatment options which are effectively treating localised and androgen-dependent PCa (ADPC) through hormonal and surgery treatments. However, over time, these cancerous cells progress to androgen-independent PCa (AIPC) which continuously grow despite hormone depletion. At this particular stage, androgen depletion therapy (ADT) is no longer effective as these cancerous cells are rendered hormone-insensitive and capable of growing in the absence of androgen. AIPC is a lethal type of disease which leads to poor prognosis and is a major contributor to PCa death rates. A natural product-derived compound, curcumin has been identified as a pleiotropic compound which capable of influencing and modulating a diverse range of molecular targets and signalling pathways in order to exhibit its medicinal properties. Due to such multi-targeted behaviour, its benefits are paramount in combating a wide range of diseases including inflammation and cancer disease. Curcumin exhibits anti-cancer properties by suppressing cancer cells growth and survival, inflammation, invasion, cell proliferation as well as possesses the ability to induce apoptosis in malignant cells. In this review, we investigate the mechanism of curcumin by modulating multiple signalling pathways such as androgen receptor (AR) signalling, activating protein-1 (AP-1), phosphatidylinositol 3-kinases/the serine/threonine kinase (PI3K/Akt/mTOR), wingless (Wnt)/ß-catenin signalling, and molecular targets including nuclear factor kappa-B (NF-κB), B-cell lymphoma 2 (Bcl-2) and cyclin D1 which are implicated in the development and progression of both types of PCa, ADPC and AIPC. In addition, the role of microRNAs and clinical trials on the anti-cancer effects of curcumin in PCa patients were also reviewed.
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Affiliation(s)
- Nurul Azwa Abd. Wahab
- Jeffrey Cheah School of Medicine and Health Science, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia; (N.A.A.W.); (I.O.)
| | - Nordin H. Lajis
- Laboratory of Natural Products, Faculty of Science, Universiti Putra Malaysia, UPM, Serdang 43400, Malaysia; (N.H.L.); (F.A.)
| | - Faridah Abas
- Laboratory of Natural Products, Faculty of Science, Universiti Putra Malaysia, UPM, Serdang 43400, Malaysia; (N.H.L.); (F.A.)
- Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, UPM, Serdang 43400, Malaysia
| | - Iekhsan Othman
- Jeffrey Cheah School of Medicine and Health Science, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia; (N.A.A.W.); (I.O.)
| | - Rakesh Naidu
- Jeffrey Cheah School of Medicine and Health Science, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia; (N.A.A.W.); (I.O.)
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Calix[4]API-s: fully functionalized calix[4]arene-based facial active pharmaceutical ingredients. Mol Divers 2020; 25:1247-1258. [PMID: 32006298 DOI: 10.1007/s11030-020-10042-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 01/22/2020] [Indexed: 01/05/2023]
Abstract
This mini-review covers 25 fully functionalized facial calix[4]arene-based symmetrical and conical cyclic tetramers with significant (comparable to established therapeutic agents) anticancer and anti-infective activities. The main role of the calixarene scaffold in these calix[4]arene-based active pharmaceutical ingredients (calix[4]API-s) is to replicate embedded phenolic units in the cyclic tetramers. So, probably owing to the multivalency, facial, conical structures of calix[4]API-s and synergistic effect of their four replicated units, they can be considered as effective bioactive agents.
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Gupta MK, Vadde R, Sarojamma V. Curcumin - A Novel Therapeutic Agent in the Prevention of Colorectal Cancer. Curr Drug Metab 2020; 20:977-987. [PMID: 31589120 DOI: 10.2174/1389200220666191007153238] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 08/11/2019] [Accepted: 09/04/2019] [Indexed: 12/14/2022]
Abstract
Background:
Colorectal cancer is the third important cause of cancer-associated deaths across the world.
Hence, there is an urgent need for understanding the complete mechanism associated with colorectal cancer, which in
turn can be utilized toward early detection as well as the treatment of colorectal cancer in humans. Though colorectal
cancer is a complex process and chemotherapy is the first step toward the treatment of colorectal cancer, recently
several studies suggested that dietary phytochemicals may also aid significantly in reducing colorectal cancer risk in
human. However, only few phytochemicals, specifically curcumin derived from the rhizomes of Curcuma longa,
have better chemotherapeutic property, which might be because of its ability to regulate the activity of key factors
associated with the initiation, promotion, as well as progression of tumors.
Objectives:
In the present review, the authors made an attempt to summarize the physiochemical properties of curcumin,
which in turn prevent colorectal cancer via regulating numerous cell signaling as well as genetic pathways.
Conclusions:
Accumulated evidence suggested that curcumin suppresses tumour/colon cancer in various ways, (a)
restricting cell cycle progression, or stimulating apoptosis, (b) restricting angiogenesis, anti-apoptotic proteins expression,
cell survival signaling pathways & their cross-communication and (c) regulating immune responses. The
information discussed in the present review will be useful in the drug discovery process as well as the treatment and
prevention of colorectal cancer in humans.
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Affiliation(s)
- Manoj K. Gupta
- Department of Biotechnology & Bioinformatics, Yogi Vemana University, Kadapa 516003, A.P, India
| | - Ramakrishna Vadde
- Department of Biotechnology & Bioinformatics, Yogi Vemana University, Kadapa 516003, A.P, India
| | - Vemula Sarojamma
- Department of Microbiology, Sri Venkateswara Medical College, Tirupathi 517501, A.P, India
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Nanotechnology-based formulations for resveratrol delivery: Effects on resveratrol in vivo bioavailability and bioactivity. Colloids Surf B Biointerfaces 2019; 180:127-140. [DOI: 10.1016/j.colsurfb.2019.04.030] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 04/09/2019] [Accepted: 04/13/2019] [Indexed: 01/05/2023]
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Madadi NR, Penthala NR, Ketkar A, Eoff RL, Trujullo-Alonso V, Guzman ML, Crooks PA. Synthesis and Evaluation of 2-Naphthaleno trans-Stilbenes and Cyanostilbenes as Anticancer Agents. Anticancer Agents Med Chem 2019; 18:556-564. [PMID: 28403783 DOI: 10.2174/1871521409666170412115703] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Revised: 03/01/2017] [Accepted: 04/04/2017] [Indexed: 01/08/2023]
Abstract
BACKGROUND Naphthalene is a good structural replacement for the isovanillin moiety (i.e. the 3- hydroxy-4-methoxyphenyl unit) in the combretastatin A-4 molecule, a natural product structurally related to resveratrol, which consistently led to the generation of highly cytotoxic naphthalene analogues when combined with a 3,4,5-trimethoxyphenyl or related aromatic system. Also, the naphthalene ring system is present in many current drug molecules that are utilized for anti-tumor, anti-arrhythmia and antioxidant therapy. OBJECTIVE In our continuing quest to improve the potencies of naturally occurring anti-cancer molecules through chemical modification, we have now synthesized a small library of 2-naphthaleno trans- stilbenes and cyanostilbenes that are structurally related to both resveratrol and DMU-212, and have evaluated these novel analogs against a panel of 54 human tumor cell lines. METHOD A series of 2-naphthaleno-containing trans-stilbenes 3a-3h (Scheme 1) were synthesized by Wittig reaction of a variety of aromatic substituted benzyl-triphenylphosphonium bromide reactants with 2- naphthaldehyde using n-BuLi as a base in THF. A second series of 2-naphthaleno trans-cyanostilbenes analogs 5a-5h was synthesized by reaction of 2-naphthaldehyde (2; 1 mmol) with an appropriately substituted 2- phenylacrylonitrile 4a-4h; 1 mmol) in 5% sodium methoxide/methanol. The reaction mixture was stirred at room temperature for 2-3 hours and the reaction allowed to go to completion (TLC monitoring), during which time the desired product precipitated out of the solution as a solid. The resulting precipitate was filtered off, washed with water and dried to yield the desired compound in yields ranging from 70-95% (Scheme 2). RESULTS The percentage growth inhibition of 54 human cancer cell lines in a primary NCI screen after exposure to compounds 3a, 3d, 5b and 5c was carried out. The results showed that only compounds 5b and 5c met the criteria for subsequent testing to determine growth inhibition values (GI50) in dose-response studies. At 10-5 M concentration, compounds 5b and 5c exhibited cytotoxic activity against leukemia cell lines HL-60(TB) and SR, lung cancer cell line NCI-H522, colon cancer cell lines COLO 205 and HCT-116, CNS-cancer cell line SF-539, melanoma cell line MDA-MB-435, and breast cancer cell line BT-549. The naphthalene trans-stilbene analogue 3a, exhibited significant growth inhibition against only one cell line, melanoma cell line MDA-MB-435 (96 % growth inhibition). Compound 3d was inactive in the 10-5 M single dose screen. CONCLUSION We have synthesized a small set of novel 2-naphthaleno stilbenes and cyanostilbenes and evaluated several of these compounds for their anticancer properties against a panel of 54 human tumor cell lines. The most active analogs, 5b and 5c, showed significantly improved growth inhibition against the human cancer cells in the NCI panel when compared to DMU-212. Of these compounds, analog 5c was found to be the most potent anticancer agent and exhibited significant growth inhibitory effects against COLO 205, CNS SF 539 and melanoma SK-MEL 5 and MDA-MB-435 cell lines with GI50 values ≤ 25 nM. Analog 5b also exhibited GI50 values in the range 25-41 nM against CNS SF 295 and melanoma MDA-MB-435 and UACC-62 cell lines. Compounds 5b and 5c were also cytotoxic towards the MV4-11 leukemia cell line with LD50 value of 450 nM and 200 nM, respectively, and demonstrated >50% inhibition of tubulin polymerization at concentrations below their LD50 values in these cells. In silico docking studies suggest that compounds 5b and 5c bind favorably at the colchicine- binding pocket of the tubulin dimer, indicating that both 5b and 5c may inhibit tubulin polymerization through a mechanism similar to that exhibited by colchicine. Derivative 5c demonstrated more favorable binding based on the docking score and buried surface area, as compared to compound 5b, in agreement with the higher observed potency of 5c against a broader range of tumor cell lines. Based on these results, analog 5c is considered to be a lead compound for further optimization as a clinical candidate for treating a variety of cancers.
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Affiliation(s)
- Nikhil R Madadi
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States
| | - Narsimha R Penthala
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States
| | - Amit Ketkar
- Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, United States
| | - Robert L Eoff
- Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, United States
| | | | - Monica L Guzman
- Weill Cornell Medical College, New York, NY 10021, United States
| | - Peter A Crooks
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States
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Frolova TS, Lipeeva AV, Baev DS, Baiborodin SI, Orishchenko КE, Kochetov AV, Sinitsyna OI. Fluorescent labeling of ursolic acid with FITC for investigation of its cytotoxic activity using confocal microscopy. Bioorg Chem 2019; 87:876-887. [PMID: 30538052 DOI: 10.1016/j.bioorg.2018.11.052] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Revised: 11/26/2018] [Accepted: 11/29/2018] [Indexed: 11/17/2022]
Abstract
Fluorescent labeling is a widely-used approach in the study of intracellular processes. This method is becoming increasingly popular for studying small bioactive molecules of natural origin; it allows us to estimate the vital intracellular changes which occur under their influence. We propose a new approach for visualization of the intracellular distribution of triterpene acids, based on fluorescent labeling by fluoresceine isothiocyanate. As a model compound we took the most widely-used and best-studied acid in the ursane series - ursolic acid, as this enabled us to compare the results obtained during our research with the available data, in order to evaluate the validity of the proposed method. Experimental tracing of the dynamics of penetration and distribution of the labeled ursolic acid has shown that when the acid enters the cell, it initially localizes on the inner membranes where the predicted target Akt1/protein kinase B - a protein that inhibits apoptosis - is located.
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Affiliation(s)
- Tatiana S Frolova
- Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, 10, Lavrentyev Ave., 630090 Novosibirsk, Russia; Novosibirsk Institute of Organic Chemistry of Siberian Branch of the Russian Academy of Sciences, 10, Lavrentyev Ave., 630090 Novosibirsk, Russia; Novosibirsk State University, 2, Pirogov Street, 630090 Novosibirsk, Russia; Federal Research Center of Fundamental and Translational Medicine of Siberian Branch of the Russian Academy of Sciences, 2, Timakov Street, 630117 Novosibirsk, Russia.
| | - Alla V Lipeeva
- Novosibirsk Institute of Organic Chemistry of Siberian Branch of the Russian Academy of Sciences, 10, Lavrentyev Ave., 630090 Novosibirsk, Russia
| | - Dmitry S Baev
- Novosibirsk Institute of Organic Chemistry of Siberian Branch of the Russian Academy of Sciences, 10, Lavrentyev Ave., 630090 Novosibirsk, Russia; Novosibirsk State University, 2, Pirogov Street, 630090 Novosibirsk, Russia
| | - Sergey I Baiborodin
- Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, 10, Lavrentyev Ave., 630090 Novosibirsk, Russia
| | - Кonstantin E Orishchenko
- Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, 10, Lavrentyev Ave., 630090 Novosibirsk, Russia
| | - Alexey V Kochetov
- Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, 10, Lavrentyev Ave., 630090 Novosibirsk, Russia; Novosibirsk State University, 2, Pirogov Street, 630090 Novosibirsk, Russia
| | - Olga I Sinitsyna
- Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, 10, Lavrentyev Ave., 630090 Novosibirsk, Russia; Novosibirsk State University, 2, Pirogov Street, 630090 Novosibirsk, Russia
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Guo R, Li Y, Wang Z, Bai H, Duan J, Wang S, Wang L, Wang J. Hypoxia-inducible factor-1α and nuclear factor-κB play important roles in regulating programmed cell death ligand 1 expression by epidermal growth factor receptor mutants in non-small-cell lung cancer cells. Cancer Sci 2019; 110:1665-1675. [PMID: 30844110 PMCID: PMC6500984 DOI: 10.1111/cas.13989] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 02/18/2019] [Accepted: 02/27/2019] [Indexed: 12/18/2022] Open
Abstract
Some driver gene mutations, including epidermal growth factor receptor (EGFR), have been reported to be involved in expression regulation of the immunosuppressive checkpoint protein programmed cell death ligand 1 (PD-L1), but the underlying mechanism remains obscure. We investigated the potential role and precise mechanism of EGFR mutants in PD-L1 expression regulation in non-small-cell lung cancer (NSCLC) cells. Examination of pivotal EGFR signaling effectors in 8 NSCLC cell lines indicated apparent associations between PD-L1 overexpression and phosphorylation of AKT and ERK, especially with increased protein levels of phospho-IκBα (p-IκBα) and hypoxia-inducible factor-1α (HIF-1α). Flow cytometry results showed stronger membrane co-expression of EGFR and PD-L1 in NSCLC cells with EGFR mutants compared with cells carrying WT EGFR. Additionally, ectopic expression or depletion of EGFR mutants and treatment with EGFR pathway inhibitors targeting MEK/ERK, PI3K/AKT, mTOR/S6, IκBα, and HIF-1α indicated strong accordance among protein levels of PD-L1, p-IκBα, and HIF-1α in NSCLC cells. Further treatment with pathway inhibitors significantly inhibited xenograft tumor growth and p-IκBα, HIF-1α, and PD-L1 expression of NSCLC cells carrying EGFR mutant in nude mice. Moreover, immunohistochemical analysis revealed obviously increased protein levels of p-IκBα, HIF-1α, and PD-L1 in NSCLC tissues with EGFR mutants compared with tissues carrying WT EGFR. Non-small-cell lung cancer tissues with either p-IκBα or HIF-1α positive staining were more likely to possess elevated PD-L1 expression compared with tissues scored negative for both p-IκBα and HIF-1α. Our findings showed important roles of phosphorylation activation of AKT and ERK and potential interplay and cooperation between NF-κB and HIF-1α in PD-L1 expression regulation by EGFR mutants in NSCLC.
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Affiliation(s)
- Rong Guo
- Department of Medical OncologyCancer Hospital, Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingChina
| | - Yong Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education)Department of Laboratory AnimalPeking University Cancer Hospital and InstituteBeijingChina
| | - Zhijie Wang
- Department of Medical OncologyCancer Hospital, Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingChina
| | - Hua Bai
- Department of Medical OncologyCancer Hospital, Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingChina
| | - Jianchun Duan
- Department of Medical OncologyCancer Hospital, Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingChina
| | - Shuhang Wang
- Department of Medical OncologyCancer Hospital, Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingChina
| | - Lvhua Wang
- Department of Radiation TherapyCancer Hospital, Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingChina
| | - Jie Wang
- Department of Medical OncologyCancer Hospital, Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingChina
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Bommagani S, Penthala NR, Balasubramaniam M, Kuravi S, Caldas-Lopes E, Guzman ML, Balusu R, Crooks PA. A novel tetrazole analogue of resveratrol is a potent anticancer agent. Bioorg Med Chem Lett 2018; 29:172-178. [PMID: 30528695 DOI: 10.1016/j.bmcl.2018.12.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 11/26/2018] [Accepted: 12/04/2018] [Indexed: 12/27/2022]
Abstract
A series of novel tetrazole analogues of resveratrol were synthesized and evaluated for their anti-leukemic activity against an extensive panel of human cancer cell lines and against the MV4-11 AML cell line. These molecules were designed as drug-like derivatives of the resveratrol analogue DMU-212 and its cyano derivatives. Four compounds 8g, 8h, 10a and 10b exhibited LD50 values of 4.60 µM, 0.02 µM, 1.46 µM, and 1.08 µM, respectively, against MV4-11 leukemia cells. The most potent compounds, 8h and 10b, were also found to be active against an extensive panel of human hematological and solid tumor cell lines; compound 8h was the most potent compound with GI50 values <10 nM against more than 90% of the human cancer cell lines in the 60-cell panel. Analogues 8g, 8h, 10a and 10b were also tested for their ability to inhibit the polymerization of tubulin, and compound 8h was found to be the most potent analogue. Molecular modeling studies demonstrated that 8h binds to the colchicine binding site on tubulin. Thus, compound 8h is considered to be a lead druglike molecule from this tetrazole series of compounds.
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Affiliation(s)
- Shobanbabu Bommagani
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Narsimha Reddy Penthala
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Meenakshisundaram Balasubramaniam
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Department of Geriatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Sudhakiranmayi Kuravi
- Department of Hematology and Oncology, University of Kansas Medical Center, KS 66160, USA
| | - Eloisi Caldas-Lopes
- Division of Hematology & Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Monica L Guzman
- Division of Hematology & Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Ramesh Balusu
- Department of Hematology and Oncology, University of Kansas Medical Center, KS 66160, USA
| | - Peter A Crooks
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
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Yang JY, Zhong X, Kim SJ, Kim DH, Kim HS, Lee JS, Yum HW, Lee J, Na HK, Surh YJ. Comparative Effects of Curcumin and Tetrahydrocurcumin on Dextran Sulfate Sodium-induced Colitis and Inflammatory Signaling in Mice. J Cancer Prev 2018; 23:18-24. [PMID: 29629345 PMCID: PMC5886491 DOI: 10.15430/jcp.2018.23.1.18] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 03/10/2018] [Accepted: 03/12/2018] [Indexed: 12/13/2022] Open
Abstract
Background Curcumin, a yellow ingredient of turmeric (Curcuma longa Linn, Zingiberaceae), has long been used in traditional folk medicine in the management of inflammatory disorders. Although curcumin has been reported to inhibit experimentally-induced colitis and carcinogenesis, the underlying molecular mechanisms remain largely unresolved. Methods Murine colitis was induced by dextran sulfate sodium (DSS) which mimics inflammatory bowel disease. Curcumin or tetrahydrocurcumin was given orally (0.1 or 0.25 mmol/kg body weight daily) for 7 days before and together with DSS administration (3% in tap water). Collected colon tissue was used for histologic and biochemical analyses. Results Administration of curcumin significantly attenuated the severity of DSS-induced colitis and the activation of NF-κB and STAT3 as well as expression of COX-2 and inducible nitric oxide synthase. In contrast to curcumin, its non-electrophilic analogue, tetrahydrocurcumin has much weaker inhibitory effects. Conclusions Intragastric administration of curcumin inhibited the experimentally induced murine colitis, which was associated with inhibition of pro-inflammatory signaling mediated by NF-κB and STAT3.
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Affiliation(s)
- Joon-Yeop Yang
- Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Xiancai Zhong
- Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Su-Jung Kim
- Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Do-Hee Kim
- Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Hyun Soo Kim
- Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Jeong-Sang Lee
- Department of Functional Food and Biotechnology, College of Medical Science, Jeonju University, Jeonju, Korea
| | - Hye-Won Yum
- Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Jeewoo Lee
- Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Hye-Kyung Na
- Department of Food Science and Biotechnology, College of Knowledge-based Services Engineering, Sungshin Women's University, Seoul, Korea
| | - Young-Joon Surh
- Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, Korea
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Aumeeruddy MZ, Zengin G, Mahomoodally MF. A review of the traditional and modern uses of Salvadora persica L. (Miswak): Toothbrush tree of Prophet Muhammad. JOURNAL OF ETHNOPHARMACOLOGY 2018; 213:409-444. [PMID: 29196134 DOI: 10.1016/j.jep.2017.11.030] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Revised: 11/25/2017] [Accepted: 11/26/2017] [Indexed: 06/07/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Salvadora persica L., also known as Arak (in Arabic) and Peelu (in Urdu), is the most common traditional source of tooth or chewing stick (miswak) highly recommended by Prophet Muhammad. To date, extensive studies have probed primarily into the validation of its traditional uses in oral care. Nonetheless, there is still a dearth of updated compilation and critical analysis of other potential ethnopharmacological properties of S. persica. This review therefore aims to provide an up-to-date detailed structured description of the traditional uses of S. persica and a critical analysis of its modern uses, highlighting its phytochemistry, pharmacological properties, and bioapplications. MATERIALS AND METHODS Various databases (Science Direct, PubMed, Wiley Online Library, and Google Scholar), books, and relevant primary sources were probed, surveyed, analysed, and included in this review. The literature cited in this review dated from 1979 to 2017. RESULTS S. persica was found to possess a plethora of bioactive compounds and broad pharmacological properties, including antimicrobial, antioxidant, enzyme inhibitory activity, antiulcer, anticonvulsant, sedative, analgesic, anti-inflammatory, hypoglycemic, hypolipidemic, antiosteoporosis, and antitumor activities. Studies also revealed the potential use of S. persica as a natural food preservative and a novel functional food ingredient. In addition, improvement in growth and reproductive performances have been observed by the introduction of S. persica in animal feed. Lastly, S. persica has also been used in the green synthesis of nanoparticles showing potential biotechnological applications. CONCLUSION S. persica showed a wide scope of application and its uses have been extended far beyond the initial traditional uses of its roots, stems, and twigs in oral care. We found a number of other ethnopharmacological uses and potential bioapplications of different parts of S. persica that warrants further investigations. Though widely studied using several in vitro and in vivo models, and tested clinically for oral hygiene mainly, several gaps and research priorities have been identified which needs to be addressed in future.
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Affiliation(s)
| | - Gokhan Zengin
- Department of Biology, Science Faculty, Selcuk University, 42250 Konya, Turkey
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Inhibition of RAD51 by siRNA and Resveratrol Sensitizes Cancer Stem Cells Derived from HeLa Cell Cultures to Apoptosis. Stem Cells Int 2018; 2018:2493869. [PMID: 29681946 PMCID: PMC5846439 DOI: 10.1155/2018/2493869] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2017] [Revised: 07/13/2017] [Accepted: 07/27/2017] [Indexed: 12/28/2022] Open
Abstract
Cervical cancer is the second most frequent tumor type in women worldwide with cases developing clinical recurrence, metastasis, and chemoresistance. The cancer stem cells (CSC) may be implicated in tumor resistance to therapy. RESveratrol (RES), a natural compound, is an antioxidant with multiple beneficial activities. We previously determined that the expression of RAD51 is decreased by RES. The aim of our study was to examine molecular mechanism by which CSC from HeLa cultures exhibit chemoresistance. We hypothesized CSC repair more efficiently DNA breaks and that RAD51 plays an important role in this mechanism. We found that CSC, derived from cervical cancer cell lines, overexpress RAD51 and are less sensitive to Etoposide (VP16). We inhibited RAD51 in CSC-enriched cultures using RES or siRNA against RAD51 messenger RNA and observed a decrease in cell viability and induction of apoptosis when treated simultaneously with VP16. In addition, we found that inhibition of RAD51 expression using RES also sensitizes CSC to VP16 treatment. Our results suggest that resveratrol is effective to sensitize cervical CSC because of RAD51 inhibition, targeting high RAD51 expressing CD49f-positive cells, which supports the possible therapeutic application of RES as a novel agent to treat cancer.
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Ferri C, West K, Otero K, Kim YH. Effectiveness of Curcumin for Treating Cancer During Chemotherapy. ACTA ACUST UNITED AC 2018. [DOI: 10.1089/act.2017.29147.yhk] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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Zou Y, Yan C, Liu JC, Huang ZJ, Xu JY, Zhou JP, Zhang HB, Zhang YH. Synthesis and anti-hepatocellular carcinoma activity of novel O 2-vinyl diazeniumdiolate-based nitric oxide-releasing derivatives of oleanolic acid. Chin J Nat Med 2018; 15:928-937. [PMID: 29329650 DOI: 10.1016/s1875-5364(18)30009-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Indexed: 11/19/2022]
Abstract
Considering that high levels of nitric oxide (NO) exert anti-cancer effect and the derivatives of oleanolic acid (OA) have shown potent anti-cancer activity, new O2-vinyl diazeniumdiolate-based NO releasing derivatives (5a-l, 11a-l) of OA were designed, synthesized, and biologically evaluated in the present study. These derivatives could release different amounts of NO in liver cells. Among them, 5d, 5i, 5j, 11g, 11h, and 11j released more NO in SMMC-7721 cells and displayed stronger proliferative inhibition against SMMC-7721 and HepG2 cells than OA and other tested compounds. The most active compound 5j showed almost 20-fold better solubility than OA in aqueous solution, released larger amounts of NO in liver cancer cells than that in normal ones, and exhibited potent anti-hepatocellular carcinoma activity but little effect on the normal liver cells. The inhibitory activity against the cancer cells was significantly diminished upon addition of an NO scavenger, suggesting that NO may contribute, at least in part, to the activity of 5j.
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Affiliation(s)
- Yu Zou
- State Key Laboratory of National Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China
| | - Chang Yan
- State Key Laboratory of National Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China
| | - Jing-Chao Liu
- State Key Laboratory of National Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China
| | - Zhang-Jian Huang
- State Key Laboratory of National Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China.
| | - Jin-Yi Xu
- State Key Laboratory of National Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China
| | - Jin-Pei Zhou
- State Key Laboratory of National Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China
| | - Hui-Bin Zhang
- State Key Laboratory of National Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China.
| | - Yi-Hua Zhang
- State Key Laboratory of National Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China.
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Mokhamatam RB, Sahoo BK, Manna SK. Suppression of microphthalmia-associated transcription factor, but not NF-kappa B sensitizes melanoma specific cell death. Apoptosis 2018; 21:928-40. [PMID: 27325430 DOI: 10.1007/s10495-016-1260-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Mutation in B-Raf leads to gain of function in melanoma and causes aggressive behavior for proliferation. Most of the therapeutics are ineffective in this scenario. However, regulation of this aggressive behavior by targeting the key molecules would be viable strategy to develop novel and effective therapeutics. In this report we provide evidences that the resveratrol is potent to regulate melanoma cell growth than other inducers of apoptosis. Resveratrol inhibits pronounced cell proliferation in melanoma than other tumor cell types. Cell cycle analysis using flow cytometry shows that the treatment with resveratrol results in S phase arrest. Resveratrol inhibits microphthalmia-associated transcription factor (MITF) and its dependent genes without interfering the MITF DNA binding in vitro. Resveratrol-mediated cell death is protected in MITF overexpressed cells and it is aggravated in MITF knocked down cells. These suggest the resveratrol-mediated decrease in MITF is the possible cause of melanoma cell death. Though resveratrol-mediated downregulation of NF-κB is responsible for cell apoptosis, but the downregulation of MITF is the main reason for melanoma-specific cell death. Thus, resveratrol can be effective chemotherapeutic agent against rapid proliferative melanoma cells.
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Affiliation(s)
- Raveendra B Mokhamatam
- Laboratory of Immunology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, Telangana, 500 001, India.,Graduate studies, Manipal University, Manipal, Karnataka, 576104, India
| | - Binay K Sahoo
- Laboratory of Immunology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, Telangana, 500 001, India
| | - Sunil K Manna
- Laboratory of Immunology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, Telangana, 500 001, India.
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Martucciello S, Paolella G, Muzashvili T, Skhirtladze A, Pizza C, Caputo I, Piacente S. Steroids from Helleborus caucasicus reduce cancer cell viability inducing apoptosis and GRP78 down-regulation. Chem Biol Interact 2018; 279:43-50. [DOI: 10.1016/j.cbi.2017.11.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Revised: 10/07/2017] [Accepted: 11/01/2017] [Indexed: 11/26/2022]
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Frolova TS, Lipeeva AV, Baev DS, Tsepilov YA, Sinitsyna OI. Apoptosis as the basic mechanism of cytotoxic action of ursolic and pomolic acids in glioma cells. Mol Biol 2017. [DOI: 10.1134/s0026893317050090] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Jaksevicius A, Carew M, Mistry C, Modjtahedi H, Opara EI. Inhibitory Effects of Culinary Herbs and Spices on the Growth of HCA-7 Colorectal Cancer Cells and Their COX-2 Expression. Nutrients 2017; 9:nu9101051. [PMID: 28934138 PMCID: PMC5691668 DOI: 10.3390/nu9101051] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 08/31/2017] [Accepted: 09/18/2017] [Indexed: 01/05/2023] Open
Abstract
It is unclear if the anti-inflammatory properties of culinary herbs and spices (CHS) are linked to their ability to inhibit Colorectal cancer cell (CRC) growth. Furthermore, their therapeutic potential with regards to CRC is unknown. The aim of this study was to establish if the inhibition of HCA-7 CRC cell growth by a selection of culinary herbs and spices (CHS) is linked to the inhibition of the cells’ cyclooxygenase-2 (COX-2 )expression, and to investigate their therapeutic potential. CHS inhibited the growth of Human colon adenocarcinoma-7 (HCA-7) cells; the order of potency was turmeric, bay leaf, ginger, sage, and rosemary; their combinations had a synergistic or additive effect on cell growth inhibition. CHS also inhibited COX-2 expression and activity; this action was comparable to that of the specific COX-2 inhibitor Celecoxib. Coincident with COX-2 inhibition was the accumulation of cells in the sub G1 phase of the HCA-7’s cell cycle and, using bay leaf and turmeric, the cleavage of caspase 3 and poly (ADP-ribose) polymerase (PARP). This latter effect showed that the effect of these CHS on growth arrest was irreversible, and was comparable to that of the caspase activator Etoposide. This study provides evidence of a link between the inhibition of HCA-7 growth, and its COX-2 expression, by CHS, and their therapeutic potential.
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Affiliation(s)
- Andrius Jaksevicius
- School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames KT1 2EE, UK.
| | - Mark Carew
- School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames KT1 2EE, UK.
| | - Calli Mistry
- School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames KT1 2EE, UK.
| | - Helmout Modjtahedi
- School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames KT1 2EE, UK.
| | - Elizabeth I Opara
- School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames KT1 2EE, UK.
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Fadus MC, Lau C, Bikhchandani J, Lynch HT. Curcumin: An age-old anti-inflammatory and anti-neoplastic agent. J Tradit Complement Med 2017; 7:339-346. [PMID: 28725630 PMCID: PMC5506636 DOI: 10.1016/j.jtcme.2016.08.002] [Citation(s) in RCA: 176] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Accepted: 08/09/2016] [Indexed: 01/19/2023] Open
Abstract
Curcumin is a natural anti-inflammatory agent that has been used for treating medical conditions for many years. Several experimental and pharmacologic trials have demonstrated its efficacy in the role as an anti-inflammatory agent. Curcumin has been shown to be effective in treating chronic conditions like rheumatoid arthritis, inflammatory bowel disease, Alzheimer's and common malignancies like colon, stomach, lung, breast, and skin cancers. As treatments in medicine become more and more complex, the answer may be something simpler. This is a review article written with the objective to systematically analyze the wealth of information regarding the medical use of curcumin, the "curry spice", and to understand the existent gaps which have prevented its widespread application in the medical community.
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Affiliation(s)
- Matthew C. Fadus
- Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States
| | - Cecilia Lau
- Duke University, Department of Psychiatry, Durham, NC, United States
| | - Jai Bikhchandani
- Creighton University, Department of Preventive Medicine, Omaha, NE 68178, United States
| | - Henry T. Lynch
- Creighton University, Department of Preventive Medicine, Omaha, NE 68178, United States
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Regulation of miRNAs by herbal medicine: An emerging field in cancer therapies. Biomed Pharmacother 2016; 86:262-270. [PMID: 28006752 DOI: 10.1016/j.biopha.2016.12.023] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Revised: 11/29/2016] [Accepted: 12/05/2016] [Indexed: 12/12/2022] Open
Abstract
MicroRNAs' expression profiles have recently gained major attention as far as cancer research is concerned. MicroRNAs are able to inhibit target gene expression via binding to the 3' UTR of target mRNA, resulting in target mRNA cleavage or translation inhibition. MicroRNAs play significant parts in a myriad of biological processes; studies have proven, on the other hand, that aberrant microRNA expression is, more often than not, associated with the growth and progression of cancers. MicroRNAs could act as oncogenes (oncomir) or tumor suppressors and can also be utilized as biomarkers for diagnosis, prognosis, and cancer therapy. Recent studies have shown that such herbal extracts as Shikonin, Sinomenium acutum, curcumin, Olea europaea, ginseng, and Coptidis Rhizoma could alter microRNA expression profiles through inhibiting cancer cell development, activating the apoptosis pathway, or increasing the efficacy of conventional cancer therapeutics. Such findings patently suggest that the novel specific targeting of microRNAs by herbal extracts could complete the restriction of tumors by killing the cancerous cells so as to recover survival results in patients diagnosed with malignancies. In this review, we summarized the current research about microRNA biogenesis, microRNAs in cancer, herbal compounds with anti-cancer effects and novel strategies for employing herbal extracts in order to target microRNAs for a better treatment of patients diagnosed with cancer.
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Basu Baul TS, Dutta D, Duthie A, Guchhait N, Rocha BGM, Guedes da Silva MFC, Mokhamatam RB, Raviprakash N, Manna SK. New dibutyltin(IV) ladders: Syntheses, structures and, optimization and evaluation of cytotoxic potential employing A375 (melanoma) and HCT116 (colon carcinoma) cell lines in vitro. J Inorg Biochem 2016; 166:34-48. [PMID: 27815980 DOI: 10.1016/j.jinorgbio.2016.10.008] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Revised: 10/05/2016] [Accepted: 10/13/2016] [Indexed: 11/16/2022]
Abstract
Synthesis and spectroscopic properties of seven new dibutyltin(IV) compounds of 2-{(E)-4-hydroxy-3-[(E)-4-(aryl)iminomethyl]phenyldiazenyl}benzoic acids (LnHH'; n=2-8) with general formula {[Bu2Sn(LnH)]2O}2 (1-7) are reported. The compounds were characterized by elemental analysis and by UV-Visible, fluorescence, IR, 1H, 13C and 119Sn NMR spectroscopies. Solid state structures of dibutyltin(IV) compounds 1-3, 6 and 7 were accomplished from single crystal X-ray crystallography which reveal the common ladder-type structure with two endo- and two exo-Sn atoms. The redox properties of LnHH' (n=2-4, 7 and 8) and their diorganotin(IV) compounds 1-3, 6 and 7 were also investigated by cyclic voltammetry. In general, the dibutyltin(IV) derivatives exhibited significant in vitro cytotoxic potency towards A375 (melanoma) and HCT116 (colon carcinoma) cell lines as determined by several experiments, like Live and Dead assay, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability assay, LDH (lactate dehydrogenase), cleavage of caspases and PARP (poly(ADP-ribose)polymerase), and DNA fragmentation. Dibutyltin(IV) compounds increase cell death without cytolysis and decreases membrane fluidity, without interfering with p53. Among the dibutyltin(IV) compounds, compound 6 was found to be the most potent, with an IC50 value of 78nM. A mechanism of action for tumor cell death is proposed.
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Affiliation(s)
- Tushar S Basu Baul
- Centre for Advanced Studies in Chemistry, North-Eastern Hill University, NEHU Permanent Campus, Umshing, Shillong 793 022, India.
| | - Dhrubajyoti Dutta
- Centre for Advanced Studies in Chemistry, North-Eastern Hill University, NEHU Permanent Campus, Umshing, Shillong 793 022, India
| | - Andrew Duthie
- School of Life & Environmental Science, Deakin University, Geelong, Victoria 3217, Australia
| | - Nikhil Guchhait
- Department of Chemistry, University of Calcutta, 92, A. P. C. Road, Calcutta 700009, India
| | - Bruno G M Rocha
- Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
| | - M Fátima C Guedes da Silva
- Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
| | | | - Nune Raviprakash
- Centre for DNA Fingerprinting & Diagnostics, Nampally, Hyderabad 500 001, India
| | - Sunil K Manna
- Centre for DNA Fingerprinting & Diagnostics, Nampally, Hyderabad 500 001, India.
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Levine CB, Bayle J, Biourge V, Wakshlag JJ. Effects and synergy of feed ingredients on canine neoplastic cell proliferation. BMC Vet Res 2016; 12:159. [PMID: 27484718 PMCID: PMC4970212 DOI: 10.1186/s12917-016-0774-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2016] [Accepted: 07/16/2016] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Adjunctive use of nutraceuticals in human cancer has shown promise, but little work has been done in canine neoplasia. Previous human research has shown that polyphenols and carotenoids can target multiple pathways in vitro and in vivo. These compounds could synergize or antagonize with currently used chemotherapies, either increasing or decreasing the effectiveness of these drugs. Considering the routine and well controlled feeding practices of most dogs, the use of nutraceuticals incorporated into pet food is attractive, pending proof that the extracts are able to improve remission rates. The aim of this study was to examine five feed ingredients for antiproliferative effects, as well as the interaction with toceranib phosphate and doxorubicin hydrochloride, when treating canine neoplastic cell lines in vitro. RESULTS Screening using MTT proliferation assays showed that green tea, turmeric, and rosemary extracts were the most effective. Turmeric extract (TE) was the most potent and exhibited synergy with a rosemary extract (RE) at concentrations from 1 to 25 μg mL(-1). This combination had an additive or synergistic effect with chemotherapeutic agents at selected concentrations within each cell line. No significant effects on cell viability were observed when the combination therapy was used with normal primary cells. CONCLUSIONS The use of turmeric and rosemary extracts in combination may be worthwhile to investigate in the pre-clinical and clinical neoplastic considering there are no negative effects on traditional chemotherapy treatment. Further studies into the pharmacokinetics and mechanisms of action of these extracts should be investigated.
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Affiliation(s)
- Corri B Levine
- Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Veterinary Medical Center C2-009, Ithaca, 14853, NY, USA
| | - Julie Bayle
- Royal Canin Research Center, Airmargues, France
| | | | - Joseph J Wakshlag
- Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Veterinary Medical Center C2-009, Ithaca, 14853, NY, USA.
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Yang PS, Wang JJ, Wang YH, Jan WC, Cheng SP, Hsu YC. 1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl] diamantane potentiates in vitro and in vivo antitumor effects of irinotecan on human colorectal cancer cells. Oncol Lett 2016; 11:3551-3557. [PMID: 27123150 DOI: 10.3892/ol.2016.4430] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2015] [Accepted: 03/10/2016] [Indexed: 11/05/2022] Open
Abstract
1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl] diamantane (DPD), a diamantane derivative, was previously noted as an anticancer compound through anticancer drug screening with NCI-60 human tumor cells. Irinotecan (CPT-11), a semisynthetic derivative of camptothecin, is clinically active in the treatment of colorectal cancer, with no cross-resistance. The current study conducted a pharmacokinetic evaluation of DPD, an essential component of drug discovery. Subsequent pathway analysis of microarray gene expression data indicated that the anticancer mechanisms of DPD were associated with cell cycle progression and apoptosis. The combined effect of DPD and CPT-11 with regard to the mechanisms of apoptosis-related pathways in COLO 205 cells, and the antitumor effects in colon cancer xenograft mice, were investigated. The plasma concentration and pharmacokinetic parameters of DPD in male albino rats were analyzed following a single dose of DPD by injection. The protein expression of active caspase-3, procaspase-3 and poly ADP-ribose polymerase (PARP) in COLO 205 cells treated with DPD and CPT-11, alone or combined, was evaluated by western blotting. A trypan blue dye exclusion assay revealed that, whilst DPD alone demonstrated good antitumor effects, this effect was potentiated when combined with CPT-11. Combined treatment with DPD and CPT-11 upregulated the expression of cleaved PARP, procaspase-3, caspase-3 and active caspase-3 in COLO 205 cells. In the colon cancer xenograft model, compared with the control (vehicle-treated) mice, the sizes of the tumors were significantly lower in mice treated with DPD and CPT-11, alone or in combination. Thus, DPD may be a potential therapeutic agent for the treatment of colorectal cancer via upregulating apoptosis-related pathways.
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Affiliation(s)
- Po-Sheng Yang
- Department of Surgery, Mackay Memorial Hospital, Taipei 10449, Taiwan R.O.C.; Department of Medicine, Mackay Medical College, New Taipei 25245, Taiwan R.O.C
| | - Jane-Jen Wang
- Department of Nursing, National Taipei University of Nursing and Health Sciences, Taipei 11219, Taiwan R.O.C
| | - Yea-Hwey Wang
- Department of Nursing, National Taipei University of Nursing and Health Sciences, Taipei 11219, Taiwan R.O.C
| | - Woan-Ching Jan
- Department of Nursing, Mackay Junior College of Medicine, Nursing and Management, Taipei 11260, Taiwan R.O.C
| | - Shih-Ping Cheng
- Department of Surgery, Mackay Memorial Hospital, Taipei 10449, Taiwan R.O.C.; Department of Medicine, Mackay Medical College, New Taipei 25245, Taiwan R.O.C
| | - Yi-Chiung Hsu
- Institute of Statistical Science, Academia Sinica, Taipei 11529, Taiwan R.O.C.; Department of Horticulture and Biotechnology, Chinese Culture University, Taipei 11114, Taiwan R.O.C
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Yousef AI, El-Masry OS, Abdel Mohsen MA. Impact of Cellular Genetic Make-up on Colorectal Cancer Cell Lines Response to Ellagic Acid: Implications of small interfering RNA. Asian Pac J Cancer Prev 2016; 17:743-8. [DOI: 10.7314/apjcp.2016.17.2.743] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Leipert J, Kässner F, Schuster S, Händel N, Körner A, Kiess W, Garten A. Resveratrol Potentiates Growth Inhibitory Effects of Rapamycin in PTEN-deficient Lipoma Cells by Suppressing p70S6 Kinase Activity. Nutr Cancer 2016; 68:342-9. [PMID: 26943752 DOI: 10.1080/01635581.2016.1145244] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Patients with phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome and germline mutations in PTEN frequently develop lipomatosis, for which there is no standard treatment. Rapamycin was shown to reduce the growth of lipoma cells with heterozygous PTEN deficiency in vitro, but concomitantly induced an upregulation of AKT phosphorylation. Since it was shown that resveratrol stabilizes PTEN, we asked whether co-incubation with resveratrol could suppress the rapamycin-induced AKT phosphorylation in PTEN-deficient lipoma cells. Resveratrol incubation resulted in decreased lipoma cell viability by inducing G1-phase cell cycle arrest and apoptosis. PTEN expression and AKT phosphorylation were not significantly changed, whereas p70S6 kinase (p70S6K) phosphorylation was reduced in PTEN-deficient lipoma cells after resveratrol incubation. Rapamycin/resveratrol co-incubation significantly decreased viability further at lower doses of resveratrol and resulted in decreased p70S6K phosphorylation compared to rapamycin incubation alone, suggesting that resveratrol potentiated the growth inhibitory effects of rapamycin by reducing p70S6K activation. Both viability and p70S6K phosphorylation of primary PTEN wild-type preadipocytes were less affected compared to PTEN-deficient lipoma cells by equimolar concentrations of resveratrol. These results support the concept of combining chemopreventive natural compounds with mammalian target of rapamycin (mTOR) inhibitors to increase the efficacy of chemotherapeutic drugs for patients suffering from overgrowth syndromes.
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Affiliation(s)
- Jenny Leipert
- a Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig , Leipzig , Germany.,b Leipzig University Medical Center, IFB Adiposity Diseases Leipzig , Leipzig , Germany
| | - Franziska Kässner
- a Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig , Leipzig , Germany
| | - Susanne Schuster
- a Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig , Leipzig , Germany
| | - Norman Händel
- a Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig , Leipzig , Germany
| | - Antje Körner
- a Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig , Leipzig , Germany.,b Leipzig University Medical Center, IFB Adiposity Diseases Leipzig , Leipzig , Germany
| | - Wieland Kiess
- a Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig , Leipzig , Germany
| | - Antje Garten
- a Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig , Leipzig , Germany
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Jiang X, Li T, Liu RH. 2α-Hydroxyursolic Acid Inhibited Cell Proliferation and Induced Apoptosis in MDA-MB-231 Human Breast Cancer Cells through the p38/MAPK Signal Transduction Pathway. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2016; 64:1806-1816. [PMID: 26872218 DOI: 10.1021/acs.jafc.5b04852] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
The mechanisms of action of 2α-hydroxyursolic acid in inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 human breast cancer cells were investigated. The antiproliferative activity and cytotoxicity were determined by the methylene blue assay. The expression of proteins was determined using Western blot. 2α-Hydroxyursolic acid significantly inhibited MDA-MB-231 cell proliferation, and no cytotoxicity was observed at concentrations below 30 μM. 2α-Hydroxyursolic acid significantly down-regulated expressions of TRAF2, PCNA, cyclin D1, and CDK4 and up-regulated the expressions of p-ASK1, p-p38, p-p53, and p-21. 2α-Hydroxyursolic acid induced apoptosis in MDA-MB-231 cells by significantly increasing the Bax/Bcl-2 ratio and inducing the cleaved caspase-3. Additionally, treatment of SB203580, a p38 MAPK specific inhibitor, reversed the inhibition of PCNA, cyclin D1, and Bcl-2 expression induced by 2α-hydroxyursolic acid in MDA-MB-231 cells. These results suggested that 2α-hydroxyursolic acid exhibited anticancer activity through the inhibition of cell proliferation and the induction of apoptosis by regulating the p38/MAPK signal transduction pathway.
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Affiliation(s)
- Xue Jiang
- Department of Food Science, 245 Stocking Hall, Cornell University , Ithaca, New York 14853-7201, United States
| | - Tong Li
- Department of Food Science, 245 Stocking Hall, Cornell University , Ithaca, New York 14853-7201, United States
| | - Rui Hai Liu
- Department of Food Science, 245 Stocking Hall, Cornell University , Ithaca, New York 14853-7201, United States
- Institute of Comparative and Environmental Toxicology, Cornell University , Ithaca, New York 14853-7201, United States
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Targeting the microRNA-21/AP1 axis by 5-fluorouracil and pirarubicin in human hepatocellular carcinoma. Oncotarget 2016; 6:2302-14. [PMID: 25544773 PMCID: PMC4385853 DOI: 10.18632/oncotarget.2955] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Accepted: 12/09/2014] [Indexed: 12/17/2022] Open
Abstract
MicroRNAs function as oncomiRs and tumor suppressors in diverse cancers. However, the utility of specific microRNAs in predicting the clinical benefit of chemotherapy has not been well-established. Here, we investigated the correlation between microRNA-21 expression and hepatic arterial infusion chemotherapy with 5-fluorouracil and pirarubicin (HAIC) for hepatocellular carcinoma (HCC). We found that HCC patients with low microRNA-21 levels in tumors tended to have a longer time to recurrence and disease-free survival. We demonstrated that microRNA-21 suppression in combination with 5-fluorouracil and pirarubicin treatment inhibited tumor growth in subcutaneous xenograft mice models. Mechanistically, the AP-1 and microRNA-21-mediated axis was verified to be a therapeutic target of cytotoxic drugs and deregulation of this axis led to an enhanced cell growth in HCC. Taken together, our findings demonstrate that microRNA-21 is a chemotherapy responsive microRNA and can serve as a prognostic biomarker for HCC patients undergoing HAIC. Targeting microRNA-21 enhances the effect of chemotherapeutic drugs, thereby suggesting that microRNA-21 suppression in combination with HAIC may be a novel approach for HCC treatment.
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Shi JJ, Jia XL, Li M, Yang N, Li YP, Zhang X, Gao N, Dang SS. Guggulsterone induces apoptosis of human hepatocellular carcinoma cells through intrinsic mitochondrial pathway. World J Gastroenterol 2015; 21:13277-13287. [PMID: 26715810 PMCID: PMC4679759 DOI: 10.3748/wjg.v21.i47.13277] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 08/24/2015] [Accepted: 10/17/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the effects of guggulsterone on the proliferation and apoptosis of human hepatoma HepG2 cells in vitro and relevant mechanisms. METHODS Human hepatocellular carcinoma HepG2 cells and normal human liver L-02 cells were treated with different concentrations of guggulsterone (5-100 μmol/L) for 24-72 h. Cell proliferation was tested by MTT assay. Cell cycle and apoptosis were investigated using flow cytometry (FACS). Bcl-2 and Bax mRNA and protein expression was detected by real-time PCR and Western blot, respectively. TGF-β1, TNF-α, and VEGF contents were determined by ELISA. RESULTS Guggulsterone significantly inhibited HepG2 cell proliferation in a dose- and time-dependent manner. FACS showed that guggulsterone arrested HepG2 cell cycle at G0/G1 phase. Guggulsterone induced apoptosis was also observed in HepG2 cells, with 24.91% ± 2.41% and 53.03% ± 2.28% of apoptotic cells in response to the treatment with 50 μmol/L and 75 μmol/L guggulsterone, respectively. Bax mRNA and protein expression was significantly increased and Bcl-2 mRNA and protein expression was decreased. ELISA analysis showed that the concentrations of TGF-β1 and VEGF were significantly decreased and TNF-α concentration was increased. CONCLUSION Guggulsterone exerts its anticancer effects by inhibiting cell proliferation and inducing apoptosis in HepG2 cells. Guggulsterone induces apoptosis by activation of the intrinsic mitochondrial pathway.
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Stone EL, Citossi F, Singh R, Kaur B, Gaskell M, Farmer PB, Monks A, Hose C, Stevens MF, Leong CO, Stocks M, Kellam B, Marlow M, Bradshaw TD. Antitumour benzothiazoles. Part 32: DNA adducts and double strand breaks correlate with activity; synthesis of 5F203 hydrogels for local delivery. Bioorg Med Chem 2015; 23:6891-9. [DOI: 10.1016/j.bmc.2015.09.052] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2015] [Revised: 09/18/2015] [Accepted: 09/30/2015] [Indexed: 11/25/2022]
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Singh M, Bhatnagar P, Mishra S, Kumar P, Shukla Y, Gupta KC. PLGA-encapsulated tea polyphenols enhance the chemotherapeutic efficacy of cisplatin against human cancer cells and mice bearing Ehrlich ascites carcinoma. Int J Nanomedicine 2015; 10:6789-809. [PMID: 26586942 PMCID: PMC4636172 DOI: 10.2147/ijn.s79489] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The clinical success of the applicability of tea polyphenols awaits efficient systemic delivery and bioavailability. Herein, following the concept of nanochemoprevention, which uses nanotechnology for enhancing the efficacy of chemotherapeutic drugs, we employed tea polyphenols, namely theaflavin (TF) and epigallocatechin-3-gallate (EGCG) encapsulated in a biodegradable nanoparticulate formulation based on poly(lactide-co-glycolide) (PLGA) with approximately 26% and 18% encapsulation efficiency, respectively. It was observed that TF/EGCG encapsulated PLGA nanoparticles (NPs) offered an up to ~7-fold dose advantage when compared with bulk TF/EGCG in terms of exerting its antiproliferative effects and also enhanced the anticancer potential of cisplatin (CDDP) in A549 (lung carcinoma), HeLa (cervical carcinoma), and THP-1 (acute monocytic leukemia) cells. Cell cycle analysis revealed that TF/EGCG-NPs were more efficient than bulk TF/EGCG in sensitizing A549 cells to CDDP-induced apoptosis, with a dose advantage of up to 20-fold. Further, TF/EGCG-NPs, alone or in combination with CDDP, were more effective in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase-9, and vascular endothelial growth factor, involved in cell proliferation, metastasis, and angiogenesis, respectively. EGCG and TF-NPs were also found to be more effective than bulk TF/EGCG in inducing the cleavage of caspase-3 and caspase-9 and Bax/Bcl2 ratio in favor of apoptosis. Further, in vivo evaluation of these NPs in combination with CDDP showed an increase in life span (P<0.05) in mice bearing Ehrlich's ascites carcinoma cells, with apparent regression of tumor volume in comparison with mice treated with bulk doses with CDDP. These results indicate that EGCG and TF-NPs have superior cancer chemosensitization activity when compared with bulk TF/EGCG.
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Affiliation(s)
- Madhulika Singh
- CSIR-Indian Institute of Toxicology Research, Lucknow, India
| | - Priyanka Bhatnagar
- CSIR-Institute of Genomics and Integrative Biology, Delhi University Campus, Delhi, India
| | - Sanjay Mishra
- CSIR-Indian Institute of Toxicology Research, Lucknow, India
| | - Pradeep Kumar
- CSIR-Institute of Genomics and Integrative Biology, Delhi University Campus, Delhi, India
| | | | - Kailash Chand Gupta
- CSIR-Indian Institute of Toxicology Research, Lucknow, India ; CSIR-Institute of Genomics and Integrative Biology, Delhi University Campus, Delhi, India
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Narayanan NK, Kunimasa K, Yamori Y, Mori M, Mori H, Nakamura K, Miller G, Manne U, Tiwari AK, Narayanan B. Antitumor activity of melinjo (Gnetum gnemon L.) seed extract in human and murine tumor models in vitro and in a colon-26 tumor-bearing mouse model in vivo. Cancer Med 2015; 4:1767-80. [PMID: 26408414 PMCID: PMC4674003 DOI: 10.1002/cam4.520] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Revised: 08/02/2015] [Accepted: 08/04/2015] [Indexed: 01/05/2023] Open
Abstract
Melinjo (Gnetum gnemon L.) seed extract (MSE) and its active ingredient gnetin C (GC), a resveratrol dimer, have been shown to possess a broad spectrum of pharmacological activities. In this study, we investigated the antitumor activity of MSE and GC using human and murine tumor cell culture models in vitro. The antitumor activity of GC was compared with trans-resveratrol (tRV), a stilbenoid polyphenol. Our results show that MSE and GC at clinically achievable concentrations significantly inhibited the proliferation of pancreatic, prostate, breast, and colon cancer cell types (P < 0.05), without affecting normal cells. Interestingly, GC exerts enhanced antitumor activity than that of tRV (P < 0.05). MSE and GC significantly induced apoptosis in all the cancer cells, indicating MSE and GC inhibit tumor cell growth by inducing apoptosis (P < 0.001). Our findings provide evidence that MSE might induce apoptosis in cancer cells via caspase-3/7-dependent and -independent mechanisms. However, GC might trigger both early and late stage apoptosis in cancer cells, at least in part by activating caspase 3/7-dependent mechanisms. Furthermore, the antitumor efficacy of MSE observed in vitro was also validated in a widely used colon-26 tumor-bearing mouse model. Oral administration of MSE at 50 and 100 mg/kg per day significantly inhibited tumor growth, intratumoral angiogenesis, and liver metastases in BALB/c mice bearing colon-26 tumors (P < 0.05). In conclusion, our findings provide evidence that MSE and GC have potent antitumor activity. Most importantly, we provide the first evidence that MSE inhibits tumor growth, intratumoral angiogenesis, and liver metastasis in a colon-26 tumor-bearing mice.
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Affiliation(s)
- Narayanan K Narayanan
- Department of Environmental Medicine, New York University School of Medicine, New York, New York
| | - Kazuhiro Kunimasa
- Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.,Institution for World Health Development, Mukogawa Women's University, Nishinomiya, Hyogo, Japan
| | - Yukio Yamori
- Institution for World Health Development, Mukogawa Women's University, Nishinomiya, Hyogo, Japan
| | - Mari Mori
- Institution for World Health Development, Mukogawa Women's University, Nishinomiya, Hyogo, Japan
| | - Hideki Mori
- Institution for World Health Development, Mukogawa Women's University, Nishinomiya, Hyogo, Japan
| | - Kazuki Nakamura
- School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan
| | - George Miller
- Departments of Surgery and Cell Biology, New York University School of Medicine, New York, New York
| | - Upender Manne
- Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Amit K Tiwari
- Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, Ohio
| | - Bhagavathi Narayanan
- Department of Environmental Medicine, New York University School of Medicine, New York, New York
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