|
1
|
Park SH, Seo JH, Kim MY, Yun HJ, Kang BK, Kim JH, Heo SV, Lee YH, Park HR, Choi MS, Lee JH. Enhanced Antitumor Activity of Korean Black Soybean Cultivar 'Soman' by Targeting STAT-Mediated Aerobic Glycolysis. Antioxidants (Basel) 2025; 14:228. [PMID: 40002413 PMCID: PMC11852074 DOI: 10.3390/antiox14020228] [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: 01/27/2025] [Revised: 02/03/2025] [Accepted: 02/08/2025] [Indexed: 02/27/2025] Open
Abstract
Black soybeans have numerous health benefits owing to their high polyphenolic content, antioxidant activity, and antitumor effects. We previously reported that the Korean black soybean cultivar 'Soman' possesses higher anthocyanin and isoflavone contents and superior antioxidant potential than other Korean black soybean cultivars and landraces (Seoritae) do. Here, we investigated and compared the antitumor effects of Soman and Seoritae and aimed to elucidate the possible mechanisms of action. Soman inhibited cancer cell proliferation and was more potent than Seoritae. Mechanistically, Soman inhibited the phosphorylation of the signal transducer and activator of transcription (STAT1, 3, and 5) in a reactive oxygen species (ROS)-independent manner, subsequently decreasing glycolytic enzyme expression and the activities of pyruvate kinase and lactate dehydrogenase. Thus, Soman suppressed glucose uptake, lactate production, and ATP production in cancer cells. Additionally, it inhibited tumor growth in a B16F10 murine melanoma syngeneic model, accompanied by reduced STAT1 phosphorylation and decreased proliferation in Soman-treated mice, more potently than observed in Seoritae-treated mice. These findings showed that Soman exerted superior antitumor activities by suppressing STAT-mediated aerobic glycolysis and proliferation. Overall, our findings demonstrate the potent, tumor-suppressive role of Soman in human cancer and uncover a novel molecular mechanism for its therapeutic effects in cancer treatment.
Collapse
Affiliation(s)
- Su Hwan Park
- Department of Health Sciences, Dong-A University, Busan 49315, Republic of Korea; (S.H.P.); (H.J.Y.)
| | - Jeong Hyun Seo
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Miryang 50424, Republic of Korea; (M.Y.K.); (B.K.K.); (J.H.K.); (S.V.H.); (Y.H.L.); (H.R.P.); (M.S.C.)
| | - Min Young Kim
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Miryang 50424, Republic of Korea; (M.Y.K.); (B.K.K.); (J.H.K.); (S.V.H.); (Y.H.L.); (H.R.P.); (M.S.C.)
| | - Hye Jin Yun
- Department of Health Sciences, Dong-A University, Busan 49315, Republic of Korea; (S.H.P.); (H.J.Y.)
| | - Beom Kyu Kang
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Miryang 50424, Republic of Korea; (M.Y.K.); (B.K.K.); (J.H.K.); (S.V.H.); (Y.H.L.); (H.R.P.); (M.S.C.)
| | - Jun Hoi Kim
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Miryang 50424, Republic of Korea; (M.Y.K.); (B.K.K.); (J.H.K.); (S.V.H.); (Y.H.L.); (H.R.P.); (M.S.C.)
| | - Su Vin Heo
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Miryang 50424, Republic of Korea; (M.Y.K.); (B.K.K.); (J.H.K.); (S.V.H.); (Y.H.L.); (H.R.P.); (M.S.C.)
| | - Yeong Hoon Lee
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Miryang 50424, Republic of Korea; (M.Y.K.); (B.K.K.); (J.H.K.); (S.V.H.); (Y.H.L.); (H.R.P.); (M.S.C.)
| | - Hye Rang Park
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Miryang 50424, Republic of Korea; (M.Y.K.); (B.K.K.); (J.H.K.); (S.V.H.); (Y.H.L.); (H.R.P.); (M.S.C.)
| | - Man Soo Choi
- Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Miryang 50424, Republic of Korea; (M.Y.K.); (B.K.K.); (J.H.K.); (S.V.H.); (Y.H.L.); (H.R.P.); (M.S.C.)
| | - Jong-Ho Lee
- Department of Health Sciences, Dong-A University, Busan 49315, Republic of Korea; (S.H.P.); (H.J.Y.)
- Department of Biomedical Sciences, Dong-A University, Busan 49315, Republic of Korea
| |
Collapse
|
|
2
|
Suzauddula M, Kobayashi K, Park S, Sun XS, Wang W. Bioengineered Anthocyanin-Enriched Tomatoes: A Novel Approach to Colorectal Cancer Prevention. Foods 2024; 13:2991. [PMID: 39335919 PMCID: PMC11430996 DOI: 10.3390/foods13182991] [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: 08/10/2024] [Revised: 09/11/2024] [Accepted: 09/18/2024] [Indexed: 09/30/2024] Open
Abstract
Colorectal cancer (CRC) remains a significant global health challenge, with barriers to effective prevention and treatment including tumor recurrence, chemoresistance, and limited overall survival rates. Anthocyanins, known for their strong anti-cancer properties, have shown promise in preventing and suppressing various cancers, including CRC. However, natural sources of anthocyanins often fail to provide sufficient quantities needed for therapeutic effects. Bioengineered crops, particularly anthocyanin-enriched tomatoes, offer a viable solution to enhance anthocyanin content. Given its large-scale production and consumption, tomatoes present an ideal target for bioengineering efforts aimed at increasing dietary anthocyanin intake. This review provides an overview of anthocyanins and their health benefits, elucidating the mechanisms by which anthocyanins modulate the transcription factors involved in CRC development. It also examines case studies demonstrating the successful bioengineering of tomatoes to boost anthocyanin levels. Furthermore, the review discusses the effects of anthocyanin extracts from bioengineered tomatoes on CRC prevention, highlighting their role in altering metabolic pathways and reducing tumor-related inflammation. Finally, this review addresses the challenges associated with bioengineering tomatoes and proposes future research directions to optimize anthocyanin enrichment in tomatoes.
Collapse
Affiliation(s)
- Md Suzauddula
- Department of Food Nutrition Dietetics and Health, Kansas State University, Manhattan, KS 66506, USA; (M.S.); (K.K.)
| | - Kaori Kobayashi
- Department of Food Nutrition Dietetics and Health, Kansas State University, Manhattan, KS 66506, USA; (M.S.); (K.K.)
| | - Sunghun Park
- Department of Horticulture and Nature Resources, Kansas State University, Manhattan, KS 66506, USA;
| | - Xiuzhi Susan Sun
- Department of Grain Science and Industry, Kansas State University, Manhattan, KS 66506, USA;
| | - Weiqun Wang
- Department of Food Nutrition Dietetics and Health, Kansas State University, Manhattan, KS 66506, USA; (M.S.); (K.K.)
| |
Collapse
|
|
3
|
Schmutz C, Plaza C, Steiger F, Stoirer N, Gufler J, Pahlke G, Will F, Berger W, Marko D. Anthocyanin-Rich Berry Extracts Affect SN-38-Induced Response: A Comparison of Non-Tumorigenic HCEC-1CT and HCT116 Colon Carcinoma Cells. Antioxidants (Basel) 2024; 13:846. [PMID: 39061915 PMCID: PMC11273996 DOI: 10.3390/antiox13070846] [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: 06/21/2024] [Revised: 07/08/2024] [Accepted: 07/11/2024] [Indexed: 07/28/2024] Open
Abstract
Chemotherapy with irinotecan (CPT-11), the pro-drug of the highly cytotoxic SN-38, is among the standard-of-care treatments for colorectal cancer. To counteract undesired toxic side effects on healthy tissue such as the intestinal epithelium, the use of preparations rich in polyphenols with anti-oxidative and anti-inflammatory properties such as anthocyanins has been proposed. In the present study, the question of whether non-tumorigenic human epithelium cells (HCEC-1CT) can be protected against the cytotoxic impact of SN-38 by anthocyanin-rich polyphenol extracts without compromising the desired therapeutic effect against tumor cells (HCT-116) was addressed. Hence, single and combinatory effects of anthocyanin-rich polyphenol extracts of elderberry (EB), bilberry (Bil), blackberry (BB) and black currant (BC) with the chemotherapeutic drug SN-38 were investigated. Out of the extracts, BB showed the most potent concentration-dependent cytotoxicity alone and in combination with SN-38, with even stronger effects in non-tumorigenic HCEC-1CT cells. In cytotoxic concentrations, BB decreased the level of DNA/topoisomerase I covalent complexes in HCEC-1CT cells below base level but without concomitant reduction in SN-38-induced DNA strand breaks. The herein reported data argue towards an interference of anthocyanins with successful treatment of cancer cells and a lack of protective properties in healthy cells.
Collapse
Affiliation(s)
- Cornelia Schmutz
- Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währingerstraße 38-40, 1090 Vienna, Austria; (C.S.); (G.P.)
- Doctoral School in Chemistry, University of Vienna, Währingerstraße 42, 1090 Vienna, Austria
| | - Crepelle Plaza
- Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währingerstraße 38-40, 1090 Vienna, Austria; (C.S.); (G.P.)
| | - Franziska Steiger
- Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währingerstraße 38-40, 1090 Vienna, Austria; (C.S.); (G.P.)
| | - Natascha Stoirer
- Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währingerstraße 38-40, 1090 Vienna, Austria; (C.S.); (G.P.)
| | - Judith Gufler
- Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währingerstraße 38-40, 1090 Vienna, Austria; (C.S.); (G.P.)
- Doctoral School in Chemistry, University of Vienna, Währingerstraße 42, 1090 Vienna, Austria
| | - Gudrun Pahlke
- Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währingerstraße 38-40, 1090 Vienna, Austria; (C.S.); (G.P.)
| | - Frank Will
- Department of Beverage Research, Hochschule Geisenheim University, P.O. Box 1154, 65366 Geisenheim, Germany;
| | - Walter Berger
- Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria;
| | - Doris Marko
- Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währingerstraße 38-40, 1090 Vienna, Austria; (C.S.); (G.P.)
| |
Collapse
|
|
4
|
Liu Y, Fernandes I, Mateus N, Oliveira H, Han F. The Role of Anthocyanins in Alleviating Intestinal Diseases: A Mini Review. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:5491-5502. [PMID: 38446808 DOI: 10.1021/acs.jafc.3c07741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/08/2024]
Abstract
Anthocyanins are phytonutrients with physiological activity belonging to the flavonoid family whose transport and absorption in the human body follow specific pathways. In the upper gastrointestinal tract, anthocyanins are rarely absorbed intact by active transporters, with most reaching the colon, where bacteria convert them into metabolites. There is mounting evidence that anthocyanins can be used for prevention and treatment of intestinal diseases, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and colorectal cancer (CRC), through the protective function on the intestinal epithelial barrier, immunomodulation, antioxidants, and gut microbiota metabolism. Dietary anthocyanins are summarized in this comprehensive review with respect to their classification and structure as well as their absorption and transport mechanisms within the gastrointestinal tract. Additionally, the review delves into the role and mechanism of anthocyanins in treating common intestinal diseases. These insights will deepen our understanding of the potential benefits of natural anthocyanins for intestinal disorders.
Collapse
Affiliation(s)
- Yang Liu
- College of Enology, Northwest A&F University, Yangling 712100, China
| | - Iva Fernandes
- LAQV, REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, Porto 4169-007 Porto, Portugal
| | - Nuno Mateus
- LAQV, REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, Porto 4169-007 Porto, Portugal
| | - Hélder Oliveira
- LAQV, REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, Porto 4169-007 Porto, Portugal
| | - Fuliang Han
- College of Enology, Northwest A&F University, Yangling 712100, China
- Shaanxi Engineering Research Center for Viti-Viniculture, Northwest A&F University, Yangling 712100, China
- Heyang Experimental Demonstration Station, Northwest A&F University, Weinan 715300, China
- Ningxia Helan Mountain's East Foothill Wine Experiment and Demonstration Station, Northwest A&F University, Yongning 750104, China
| |
Collapse
|
|
5
|
Schmutz C, Will F, Varga E, Jaunecker C, Pahlke G, Berger W, Marko D. In Vitro Inhibitory Potential of Different Anthocyanin-Rich Berry Extracts in Murine CT26 Colon Cancer Cells. Molecules 2023; 28:7684. [PMID: 38067418 PMCID: PMC10707341 DOI: 10.3390/molecules28237684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 11/15/2023] [Accepted: 11/19/2023] [Indexed: 12/18/2023] Open
Abstract
Anti-oxidant, -inflammatory, and -carcinogenic activities of bioactive plant constituents, such as anthocyanins, have been widely discussed in literature. However, the potential interaction of anthocyanin-rich extracts with routinely used chemotherapeutics is still not fully elucidated. In the present study, anthocyanin-rich polyphenol extracts of blackberry (BB), bilberry (Bil), black currant (BC), elderberry (EB), and their respective main anthocyanins (cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, cyanidin-3-O-rutinoside, and cyanidin-3-O-sambubioside) were investigated concerning their cytotoxic and DNA-damaging properties in murine CT26 cells either alone or in combination with the chemotherapeutic agent SN-38. BB exerted potent cytotoxic effects, while Bil, BC, and EB only had marginal effects on cell viability. Single anthocyanins comprised of the extracts could not induce comparable effects. Even though the BB extract further pronounced SN-38-induced cytotoxicity and inhibited cell adhesion at 100-200 µg/mL, no effect on DNA damage was observed. In conclusion, anti-carcinogenic properties of the extracts on CT26 cells could be ranked BB >> BC ≥ Bil ≈ EB. Mechanisms underlying the potent cytotoxic effects are still to be elucidated since the induction of DNA damage does not play a role.
Collapse
Affiliation(s)
- Cornelia Schmutz
- Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währingerstraße 38-40, 1090 Vienna, Austria; (C.S.); (E.V.); (G.P.)
- Doctoral School in Chemistry, University of Vienna, Währingerstraße 42, 1090 Vienna, Austria
| | - Frank Will
- Department of Beverage Research, Hochschule Geisenheim University, P.O. Box 1154, 65366 Geisenheim, Germany;
| | - Elisabeth Varga
- Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währingerstraße 38-40, 1090 Vienna, Austria; (C.S.); (E.V.); (G.P.)
| | - Carola Jaunecker
- Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria; (C.J.); (W.B.)
| | - Gudrun Pahlke
- Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währingerstraße 38-40, 1090 Vienna, Austria; (C.S.); (E.V.); (G.P.)
| | - Walter Berger
- Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria; (C.J.); (W.B.)
| | - Doris Marko
- Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währingerstraße 38-40, 1090 Vienna, Austria; (C.S.); (E.V.); (G.P.)
| |
Collapse
|
|
6
|
Macis D, Briata IM, D’Ecclesiis O, Johansson H, Aristarco V, Buttiron Webber T, Oppezzi M, Gandini S, Bonanni B, DeCensi A. Inflammatory and Metabolic Biomarker Assessment in a Randomized Presurgical Trial of Curcumin and Anthocyanin Supplements in Patients with Colorectal Adenomas. Nutrients 2023; 15:3894. [PMID: 37764678 PMCID: PMC10537228 DOI: 10.3390/nu15183894] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 09/01/2023] [Accepted: 09/05/2023] [Indexed: 09/29/2023] Open
Abstract
Colorectal cancer prevention is crucial for public health, given its high mortality rates, particularly in young adults. The early detection and treatment of precancerous lesions is key to preventing carcinogenesis progression. Natural compounds like curcumin and anthocyanins show promise in impeding adenomatous polyp progression in preclinical models. We conducted a randomized, double-blind, placebo-controlled, phase II presurgical trial in 35 patients with adenomatous polyps to explore the biological effects of curcumin and anthocyanins on circulating biomarkers of inflammation and metabolism. No significant difference in biomarker changes by treatment arm was observed. However, the network analysis before treatment revealed inverse correlations between adiponectin and BMI and glycemia, as well as direct links between inflammatory biomarkers and leptin and BMI. In addition, a considerable inverse relationship between adiponectin and grade of dysplasia was detected after treatment (corr = -0.45). Finally, a significant increase in IL-6 at the end of treatment in subjects with high-grade dysplasia was also observed (p = 0.02). The combined treatment of anthocyanins and curcumin did not result in the direct modulation of circulating biomarkers of inflammation and metabolism, but revealed a complex modulation of inflammatory and metabolic biomarkers of colon carcinogenesis.
Collapse
Affiliation(s)
- Debora Macis
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (D.M.); (H.J.); (V.A.); (B.B.)
| | - Irene Maria Briata
- Division of Medical Oncology, E.O. Galliera Hospital, 16128 Genoa, Italy; (I.M.B.); (T.B.W.)
| | - Oriana D’Ecclesiis
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy; (O.D.); (S.G.)
| | - Harriet Johansson
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (D.M.); (H.J.); (V.A.); (B.B.)
| | - Valentina Aristarco
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (D.M.); (H.J.); (V.A.); (B.B.)
| | - Tania Buttiron Webber
- Division of Medical Oncology, E.O. Galliera Hospital, 16128 Genoa, Italy; (I.M.B.); (T.B.W.)
| | - Massimo Oppezzi
- Division of Gastroenterology, E.O. Galliera Hospital, 16128 Genoa, Italy;
| | - Sara Gandini
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy; (O.D.); (S.G.)
| | - Bernardo Bonanni
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (D.M.); (H.J.); (V.A.); (B.B.)
| | - Andrea DeCensi
- Division of Medical Oncology, E.O. Galliera Hospital, 16128 Genoa, Italy; (I.M.B.); (T.B.W.)
| |
Collapse
|
|
7
|
Nascimento RDPD, Machado APDF. The preventive and therapeutic effects of anthocyanins on colorectal cancer: A comprehensive review based on up-to-date experimental studies. Food Res Int 2023; 170:113028. [PMID: 37316089 DOI: 10.1016/j.foodres.2023.113028] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Revised: 05/01/2023] [Accepted: 05/21/2023] [Indexed: 06/16/2023]
Abstract
Colorectal cancer (CRC) is the second most lethal and the third most diagnosed type of cancer worldwide. More than 75% of CRC cases are sporadic and lifestyle-related. Risk factors include diet, physical inactivity, genetics, smoking, alcohol, changes in the intestinal microbiota, and inflammation-related diseases such as obesity, diabetes, and inflammatory bowel diseases. The limits of conventional treatments (surgery, chemotherapy, radiotherapy), as demonstrated by the side effects and resistance of many CRC patients, are making professionals search for new chemopreventive alternatives. In this context, diets rich in fruits and vegetables or plant-based products, which contain high levels of phytochemicals, have been postulated as complementary therapeutic options. Anthocyanins, phenolic pigments responsible for the vivid colors of most red, purple, and blue fruits and vegetables, have been shown protective effects on CRC. Berries, grapes, Brazilian fruits, and vegetables such as black rice and purple sweet potato are examples of products rich in anthocyanins, which have been able to reduce cancer development by modulating signaling pathways associated with CRC. Therefore, this review has as main objective to present and discuss the potential preventive and therapeutic effects of anthocyanins present in fruits and vegetables, in plant extracts, or in their pure form on CRC, taking into account up-to-date experimental studies (2017-2023). Additionally, a highlight is given towards the mechanisms of action of anthocyanins on CRC.
Collapse
Affiliation(s)
- Roberto de Paula do Nascimento
- Laboratory of Nutrition and Metabolism (LANUM), Department of Food Science and Nutrition (DECAN), School of Food Engineering (FEA), University of Campinas (UNICAMP), Monteiro Lobato Street 80, 13083-862, Campinas, São Paulo, Brazil; European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Hadyn Ellis Building, Maindy Rd, CF24 4HQ, Cardiff, Wales, United Kingdom.
| | - Ana Paula da Fonseca Machado
- Study and Research Group on Agroindustrial Products from the Cerrado (GEPPAC), Faculty of Engineering (FAEN), Federal University of Grande Dourados (UFGD), Dourados-Itahum Highway Km 12, 79804-970, Dourados, Mato Grosso do Sul, Brazil.
| |
Collapse
|
|
8
|
De S, Paul S, Manna A, Majumder C, Pal K, Casarcia N, Mondal A, Banerjee S, Nelson VK, Ghosh S, Hazra J, Bhattacharjee A, Mandal SC, Pal M, Bishayee A. Phenolic Phytochemicals for Prevention and Treatment of Colorectal Cancer: A Critical Evaluation of In Vivo Studies. Cancers (Basel) 2023; 15:993. [PMID: 36765950 PMCID: PMC9913554 DOI: 10.3390/cancers15030993] [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: 12/30/2022] [Revised: 01/30/2023] [Accepted: 01/30/2023] [Indexed: 02/08/2023] Open
Abstract
Colorectal cancer (CRC) is the third most diagnosed and second leading cause of cancer-related death worldwide. Limitations with existing treatment regimens have demanded the search for better treatment options. Different phytochemicals with promising anti-CRC activities have been reported, with the molecular mechanism of actions still emerging. This review aims to summarize recent progress on the study of natural phenolic compounds in ameliorating CRC using in vivo models. This review followed the guidelines of the Preferred Reporting Items for Systematic Reporting and Meta-Analysis. Information on the relevant topic was gathered by searching the PubMed, Scopus, ScienceDirect, and Web of Science databases using keywords, such as "colorectal cancer" AND "phenolic compounds", "colorectal cancer" AND "polyphenol", "colorectal cancer" AND "phenolic acids", "colorectal cancer" AND "flavonoids", "colorectal cancer" AND "stilbene", and "colorectal cancer" AND "lignan" from the reputed peer-reviewed journals published over the last 20 years. Publications that incorporated in vivo experimental designs and produced statistically significant results were considered for this review. Many of these polyphenols demonstrate anti-CRC activities by inhibiting key cellular factors. This inhibition has been demonstrated by antiapoptotic effects, antiproliferative effects, or by upregulating factors responsible for cell cycle arrest or cell death in various in vivo CRC models. Numerous studies from independent laboratories have highlighted different plant phenolic compounds for their anti-CRC activities. While promising anti-CRC activity in many of these agents has created interest in this area, in-depth mechanistic and well-designed clinical studies are needed to support the therapeutic use of these compounds for the prevention and treatment of CRC.
Collapse
Affiliation(s)
- Samhita De
- Division of Molecular Medicine, Bose Institute, Kolkata 700 054, India
| | - Sourav Paul
- Department of Biotechnology, National Institute of Technology, Durgapur 713 209, India
| | - Anirban Manna
- Division of Molecular Medicine, Bose Institute, Kolkata 700 054, India
| | | | - Koustav Pal
- Jawaharlal Institute Post Graduate Medical Education and Research, Puducherry 605 006, India
| | - Nicolette Casarcia
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| | - Arijit Mondal
- Department of Pharmaceutical Chemistry, M.R. College of Pharmaceutical Sciences and Research, Balisha 743 234, India
| | - Sabyasachi Banerjee
- Department of Pharmaceutical Chemistry, Gupta College of Technological Sciences, Asansol 713 301, India
| | - Vinod Kumar Nelson
- Department of Pharmacology, Raghavendra Institute of Pharmaceutical Education and Research, Anantapur 515 721, India
| | - Suvranil Ghosh
- Division of Molecular Medicine, Bose Institute, Kolkata 700 054, India
| | - Joyita Hazra
- Department of Biotechnology, Indian Institute of Technology, Chennai 600 036, India
| | - Ashish Bhattacharjee
- Department of Biotechnology, National Institute of Technology, Durgapur 713 209, India
| | | | - Mahadeb Pal
- Division of Molecular Medicine, Bose Institute, Kolkata 700 054, India
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| |
Collapse
|
|
9
|
Vaneková Z, Rollinger JM. Bilberries: Curative and Miraculous - A Review on Bioactive Constituents and Clinical Research. Front Pharmacol 2022; 13:909914. [PMID: 35847049 PMCID: PMC9277355 DOI: 10.3389/fphar.2022.909914] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 05/31/2022] [Indexed: 11/13/2022] Open
Abstract
Bilberry (Vaccinium myrtillus L.) fruits are an important part of local diets in many countries and are used as a medicinal herb to treat various disorders. Extracts from fruits are often a part of eye health-promoting supplements, whereas extracts from leaves are advertised for type 2 diabetes mellitus and glycemic control. This review provides an overview of the current knowledge of the phytochemical contents of bilberry fruits and leaves and their bioactivities, critically summarizes origins of the health claims and the outcome of clinical trials, with special attention towards those published in the past 10 years. Overall, the three most referenced indications, which are type 2 diabetes mellitus, vision disorders and circulatory diseases, all include contradictory results with no clear conclusion as to the benefits and recommended dosages. Moreover, the indications for vision disorders and diabetes originate from unproven or false claims that have been repeated in research since the 20th century without consistent fact-checking. Beneficial clinical results have been attested for the treatment of dyslipidemia and chronic inflammatory disorders when applied as dietary supplementation of fresh bilberries or as anthocyanin-rich bilberry fruit extracts. However, there is a general lack of double-blinded controlled research with larger sample sizes.
Collapse
Affiliation(s)
- Zuzana Vaneková
- Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia
- Department of Pharmaceutical Sciences, Division of Pharmacognosy, University of Vienna, Vienna, Austria
| | - Judith M. Rollinger
- Department of Pharmaceutical Sciences, Division of Pharmacognosy, University of Vienna, Vienna, Austria
| |
Collapse
|
|
10
|
Comparison of chemometric strategies for potential exposure marker discovery and false-positive reduction in untargeted metabolomics: application to the serum analysis by LC-HRMS after intake of Vaccinium fruit supplements. Anal Bioanal Chem 2022; 414:1841-1855. [PMID: 35028688 DOI: 10.1007/s00216-021-03815-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/18/2021] [Accepted: 11/30/2021] [Indexed: 11/01/2022]
Abstract
Untargeted liquid chromatographic-high-resolution mass spectrometric (LC-HRMS) metabolomics for potential exposure marker (PEM) discovery in nutrikinetic studies generates complex outputs. The correct selection of statistically significant PEMs is a crucial analytical step for understanding nutrition-health interactions. Hence, in this paper, different chemometric selection workflows for PEM discovery, using multivariate or univariate parametric or non-parametric data analyses, were comparatively tested and evaluated. The PEM selection protocols were applied to a small-sample-size untargeted LC-HRMS study of a longitudinal set of serum samples from 20 volunteers after a single intake of (poly)phenolic-rich Vaccinium myrtillus and Vaccinium corymbosum supplements. The non-parametric Games-Howell test identified a restricted group of significant features, thus minimizing the risk of false-positive retention. Among the forty-seven PEMs exhibiting a statistically significant postprandial kinetics, twelve were successfully annotated as purine pathway metabolites, benzoic and benzodiol metabolites, indole alkaloids, and organic and fatty acids, and five (i.e. octahydro-methyl-β-carboline-dicarboxylic acid, tetrahydro-methyl-β-carboline-dicarboxylic acid, citric acid, caprylic acid, and azelaic acid) were associated to Vaccinium berry consumption for the first time. The analysis of the area under the curve of the longitudinal dataset highlighted thirteen statistically significant PEMs discriminating the two interventions, including four intra-intervention relevant metabolites (i.e. abscisic acid glucuronide, catechol sulphate, methyl-catechol sulphate, and α-hydroxy-hippuric acid). Principal component analysis and sample classification through linear discriminant analysis performed on PEM maximum intensity confirmed the discriminating role of these PEMs.
Collapse
|
|
11
|
Mudd AM, Gu T, Munagala R, Jeyabalan J, Fraig M, Egilmez NK, Gupta RC. Berry anthocyanidins inhibit intestinal polyps and colon tumors by modulation of Src, EGFR and the colon inflammatory environment. Oncoscience 2021; 8:120-133. [PMID: 34926717 PMCID: PMC8664094 DOI: 10.18632/oncoscience.548] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 12/01/2021] [Indexed: 11/25/2022] Open
Abstract
Colorectal cancer is the third most common form of cancer diagnosed and the third leading class for cancer-related deaths. Given the prevalence of colon cancer worldwide, further insight into developing novel and effective prevention and treatment strategies are warranted. The family of plant pigments known as the anthocyanins has been identified with a variety of health benefits including chemopreventive and therapeutic effects. A limitation to current clinical applications of anthocyanins is the high doses that are required. In order to overcome this limitation, we tested the active moiety, anthocyanidins for chemopreventive and therapeutic effects against colorectal cancer in vivo and in vitro. Treatment with native anthocyanidin mixture (Anthos) from bilberry yielded significant antiproliferative activity against colon cancer cells. Anthos treatment led to significant reductions in polyp and tumor counts in vivo. Reduced Src and EGFR phosphorylation was observed with Anthos treatment, which correlated with downstream targets such as PD-L1 and modulation of the colon inflammatory environment. These results provide a promising outlook on the impact of berry Anthos for the treatment and prevention of familial adenomatous polyposis and colorectal cancer. Results from this study also provide novel mechanistic insight into the chemopreventive and therapeutic activities of Anthos.
Collapse
Affiliation(s)
- Ashley M Mudd
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.,These authors contributed equally to this work
| | - Tao Gu
- Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202, USA.,These authors contributed equally to this work
| | - Radha Munagala
- James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.,Department of Medicine, University of Louisville, Louisville, KY 40202, USA
| | - Jeyaprakash Jeyabalan
- James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA
| | - Mostafa Fraig
- Department of Pathology and Laboratory Medicine, University of Louisville, Louisville, KY 40202, USA
| | - Nejat K Egilmez
- Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202, USA
| | - Ramesh C Gupta
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.,James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA
| |
Collapse
|
|
12
|
Briata IM, Paleari L, Rutigliani M, Petrera M, Caviglia S, Romagnoli P, Libera MD, Oppezzi M, Puntoni M, Siri G, Lazzeroni M, Howells L, Singh R, Brown K, DeCensi A. A Presurgical Study of Curcumin Combined with Anthocyanin Supplements in Patients with Colorectal Adenomatous Polyps. Int J Mol Sci 2021; 22:11024. [PMID: 34681684 PMCID: PMC8539981 DOI: 10.3390/ijms222011024] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 10/06/2021] [Accepted: 10/11/2021] [Indexed: 12/16/2022] Open
Abstract
Adenomatous polyps are precancerous lesions associated with a higher risk of colorectal cancer (CRC). Curcumin and anthocyanins have shown promising CRC-preventive activity in preclinical and epidemiological studies. The objective of this window-of-opportunity, proof-of principle trial was to evaluate the effect of curcumin combined with anthocyanin supplements on tissue biomarkers of colorectal adenomatous polyps. Eligible patients received either anthocyanin and curcumin supplementation or related matching placebo for 4-6 weeks before polyp removal. Adenomatous polyps and adjacent tissue biopsies were collected at baseline and after supplementation for immunohistochemical assessment of β-catenin, NF-kappa B (NF-κB), Ki-67, P53, and dysplasia. No differences were observed in baseline biomarker expression between normal and dysplastic tissues. The combination of anthocyanins and curcumin resulted in a significant borderline reduction of NF-κB immunohistochemistry (IHC) expression in adenoma tissue (geometric mean ratio (GMR): 0.72; 95% confidence interval (CI): 0.51-1.00; p-value: 0.05) and a trend to a reduction of Ki-67 (GMR: 0.73; 95% CI: 0.50-1.08; p-value: 0.11). No significant modulation of biomarkers in normal adjacent mucosa was observed. We concluded that the combined supplementation of anthocyanins and curcumin seems to lead to a potentially favorable modulation of tissue biomarkers of inflammation and proliferation in colon adenomas.
Collapse
Affiliation(s)
- Irene Maria Briata
- Division of Medical Oncology, E.O. Galliera Hospital, 16128 Genoa, Italy; (I.M.B.); (M.P.)
| | - Laura Paleari
- Research, Innovation and HTA, A.Li.Sa. Liguria Health Authority, 16121 Genoa, Italy
| | | | - Marilena Petrera
- Division of Medical Oncology, E.O. Galliera Hospital, 16128 Genoa, Italy; (I.M.B.); (M.P.)
| | - Silvia Caviglia
- Clinical Trial Unit, Office of the Scientific Director, E.O. Galliera Hospital, 16128 Genoa, Italy;
| | - Paola Romagnoli
- Division of Gastroenterology, E.O. Galliera Hospital, 16128 Genoa, Italy; (P.R.); (M.D.L.); (M.O.)
| | - Mauro Dalla Libera
- Division of Gastroenterology, E.O. Galliera Hospital, 16128 Genoa, Italy; (P.R.); (M.D.L.); (M.O.)
| | - Massimo Oppezzi
- Division of Gastroenterology, E.O. Galliera Hospital, 16128 Genoa, Italy; (P.R.); (M.D.L.); (M.O.)
| | - Matteo Puntoni
- Clinical & Epidemiological Research Unit, University Hospital of Parma, 43126 Parma, Italy;
| | - Giacomo Siri
- Division of Pathology, E.O. Galliera Hospital, 16128 Genoa, Italy; (M.R.); (G.S.)
| | - Matteo Lazzeroni
- Division of Cancer Prevention and Genetics, IEO European Institute of Oncology IRCCS, 20141 Milan, Italy;
| | - Lynne Howells
- Leicester Cancer Research Centre, University of Leicester, Leicester LE1 7RH, UK; (L.H.); (R.S.); (K.B.)
| | - Raj Singh
- Leicester Cancer Research Centre, University of Leicester, Leicester LE1 7RH, UK; (L.H.); (R.S.); (K.B.)
| | - Karen Brown
- Leicester Cancer Research Centre, University of Leicester, Leicester LE1 7RH, UK; (L.H.); (R.S.); (K.B.)
| | - Andrea DeCensi
- Division of Medical Oncology, E.O. Galliera Hospital, 16128 Genoa, Italy; (I.M.B.); (M.P.)
- Wolfson Institute of Preventive Medicine, Queen Mary University of London, London E1 4NS, UK
| |
Collapse
|
|
13
|
Bilberry ( Vaccinium myrtillus L.) Powder Has Anticarcinogenic Effects on Oral Carcinoma In Vitro and In Vivo. Antioxidants (Basel) 2021; 10:antiox10081319. [PMID: 34439567 PMCID: PMC8389301 DOI: 10.3390/antiox10081319] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 08/17/2021] [Accepted: 08/18/2021] [Indexed: 12/23/2022] Open
Abstract
Previous studies indicate that bilberry with high amounts of phenolic compounds can inhibit carcinogenic processes of colorectal cancer in vitro and in vivo. However, no studies have focused on the effects of bilberry on oral cancer. In this study, we aimed to examine the effects of bilberry powder on oral squamous cell carcinoma (OSCC) cells using both in vitro and in vivo assays. The effects of 0, 1, 10, and 25 mg/mL of whole bilberry powder on the viability, proliferation, migration, and invasion of OSCC (HSC-3) cells were examined and compared with 0.01 mg/mL of cetuximab. Two oral keratinocyte cell lines served as controls. Tumor area was analyzed in zebrafish microinjected with HSC-3 cells and treated with 2.5, 10, or 25 µg/mL of bilberry powder. Metastases in the head or tail areas were counted. Bilberry powder inhibited the viability, proliferation, migration, and invasion of HSC-3 cells (p < 0.05), which was more pronounced with higher concentrations. Cetuximab had no effect on HSC-3 cell migration or invasion. Compared to controls, the tumor area in zebrafish treated with bilberry powder (10 and 25 µg/mL) was reduced significantly (p = 0.038 and p = 0.021, respectively), but the number of fish with metastases did not differ between groups. Based on our in vitro and in vivo experiments, we conclude that whole bilberry powder has anti-tumor effects on OSCC cells.
Collapse
|
|
14
|
Onali T, Kivimäki A, Mauramo M, Salo T, Korpela R. Anticancer Effects of Lingonberry and Bilberry on Digestive Tract Cancers. Antioxidants (Basel) 2021; 10:antiox10060850. [PMID: 34073356 PMCID: PMC8228488 DOI: 10.3390/antiox10060850] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 05/17/2021] [Accepted: 05/21/2021] [Indexed: 12/17/2022] Open
Abstract
Wild berries are part of traditional Nordic diets and are a rich source of phytochemicals, such as polyphenols. Various berry treatments have shown to interfere with cancer progression in vitro and in vivo. Here, we systematically reviewed the anticancer effects of two Nordic wild berries of the Vaccinium genus, lingonberry (Vaccinium vitis-idaea) and bilberry (Vaccinium myrtillus), on digestive tract cancers. The review was conducted according to the PRISMA 2020 guidelines. Searches included four databases: PubMed, Scopus, Web of Science, and CAB abstracts. Publications not written in English, case-reports, reviews, and conference abstracts were excluded. Moreover, studies with only indirect markers of cancer risk or studies with single compounds not derived from lingonberry or bilberry were not included. Meta-analysis was not performed. The majority (21/26) of studies investigated bilberry and colorectal cancer. Experimental studies on colorectal cancer indicated that bilberry inhibited intestinal tumor formation and cancer cell growth. One uncontrolled pilot human study supported the inhibitory potential of bilberry on colorectal cancer cell proliferation. Data from all 10 lingonberry studies suggests potent inhibition of cancer cell growth and tumor formation. In conclusion, in vitro and animal models support the antiproliferative and antitumor effects of various bilberry and lingonberry preparations on digestive tract cancers.
Collapse
Affiliation(s)
- Tuulia Onali
- Department of Oral and Maxillofacial Diseases, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland; (T.O.); (A.K.); (T.S.)
- Medical Nutrition Physiology, Department of Pharmacology, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
- Translational Immunology Research Program (TRIMM), University of Helsinki, 00014 Helsinki, Finland
| | - Anne Kivimäki
- Department of Oral and Maxillofacial Diseases, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland; (T.O.); (A.K.); (T.S.)
- Medical Nutrition Physiology, Department of Pharmacology, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
| | - Matti Mauramo
- Department of Pathology, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland;
| | - Tuula Salo
- Department of Oral and Maxillofacial Diseases, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland; (T.O.); (A.K.); (T.S.)
- Translational Immunology Research Program (TRIMM), University of Helsinki, 00014 Helsinki, Finland
- Cancer and Translational Medicine Research Unit, University of Oulu, 90014 Oulu, Finland
- Medical Research Centre, Oulu University Hospital, 90014 Oulu, Finland
| | - Riitta Korpela
- Medical Nutrition Physiology, Department of Pharmacology, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
- Human Microbiome Research Program, University of Helsinki, 00014 Helsinki, Finland
- Correspondence:
| |
Collapse
|
|
15
|
Antiproliferative Activity on Human Colon Adenocarcinoma Cells and In Vitro Antioxidant Effect of Anthocyanin-Rich Extracts from Peels of Species of the Myrtaceae Family. Molecules 2021; 26:molecules26030564. [PMID: 33498977 PMCID: PMC7865521 DOI: 10.3390/molecules26030564] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 01/08/2021] [Accepted: 01/10/2021] [Indexed: 12/12/2022] Open
Abstract
There is a significant indication of the beneficial health effects of fruit rich diets. Fruits of native plant species have noticeably different phytochemicals and bioactive effects. The aim of this work was to characterize and compare the constituents of jabuticaba (Myrciaria jaboticaba, MJ), jamun-berry (Syzygium cumini, SC), and malay-apple (Syzygium malaccense, SM) extracts and their influence on antioxidant activity in vitro and antiproliferative effects on human colon adenocarcinoma cells. According to the results, dried peel powders (DP) have a high anthocyanin content, phenolic compounds, and antioxidant activity when compared to freeze dried extracts (FD). M. jaboticaba dried peel powder extract had a higher total anthocyanin and phenolic compounds content (802.90 ± 1.93 and 2152.92 ± 43.95 mg/100 g, respectively). A reduction in cell viability of HT-29 cells after treatment with M. jaboticaba extracts (DP-MJ and FD-MJ) was observed via MTT assay. Flow cytometry showed that the treatment with the anthocyanin-rich extracts from MJ, SC, and SM had an inhibitory impact on cell development due to G2/M arrest and caused a rise in apoptotic cells in relation to the control group. The findings of this study highlight the potential of peel powders from Myrtaceae fruits as an important source of natural antioxidants and a protective effect against colon adenocarcinoma.
Collapse
|
|
16
|
Bars-Cortina D, Sakhawat A, Piñol-Felis C, Motilva MJ. Chemopreventive effects of anthocyanins on colorectal and breast cancer: A review. Semin Cancer Biol 2021; 81:241-258. [DOI: 10.1016/j.semcancer.2020.12.013] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Revised: 12/10/2020] [Accepted: 12/11/2020] [Indexed: 02/06/2023]
|
|
17
|
Gonzalez de Mejia E, Rebollo-Hernanz M, Aguilera Y, Martín-Cabrejas MA. Role of anthocyanins in oxidative stress and the prevention of cancer in the digestive system. Cancer 2021. [DOI: 10.1016/b978-0-12-819547-5.00024-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
18
|
Oyeyinka BO, Afolayan AJ. Potentials of Musa Species Fruits against Oxidative Stress-Induced and Diet-Linked Chronic Diseases: In Vitro and In Vivo Implications of Micronutritional Factors and Dietary Secondary Metabolite Compounds. Molecules 2020; 25:E5036. [PMID: 33142997 PMCID: PMC7663138 DOI: 10.3390/molecules25215036] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 09/10/2020] [Accepted: 09/23/2020] [Indexed: 12/12/2022] Open
Abstract
Nutritional quality and the well-being of the body system are directly linked aspects of human survival. From the unborn foetus to adulthood, the need for sustainable access to micronutrient-rich foods is pertinent and the global consumption of banana and plantain fruits, in effect, contributes to the alleviation of the scourge of malnutrition. This review is particularly aimed at evaluating the pharmacological dimensions through the biological mechanisms of Musa fruits in the body, which represent correlations with their constituent micronutrient factors and dietary polyphenolic constituents such as minerals, vitamin members, anthocyanins, lutein, α-,β- carotenes, neoxanthins and cryptoxanthins, epi- and gallo catechins, catecholamines, 3-carboxycoumarin, β-sitosterol, monoterpenoids, with series of analytical approaches for the various identified compounds being highlighted therein. Derivative value-products from the compartments (flesh and peel) of Musa fruits are equally highlighted, bringing forth the biomedicinal and nutritional relevance, including the potentials of Musa species in dietary diversification approaches.
Collapse
Affiliation(s)
| | - Anthony Jide Afolayan
- Medicinal Plants and Economic Development (MPED) Research Centre, Department of Botany, University of Fort Hare, Alice 5700, South Africa;
| |
Collapse
|
|
19
|
Lagoa R, Marques-da-Silva D, Diniz M, Daglia M, Bishayee A. Molecular mechanisms linking environmental toxicants to cancer development: Significance for protective interventions with polyphenols. Semin Cancer Biol 2020; 80:118-144. [PMID: 32044471 DOI: 10.1016/j.semcancer.2020.02.002] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 01/25/2020] [Accepted: 02/01/2020] [Indexed: 12/12/2022]
Abstract
Human exposure to environmental toxicants with diverse mechanisms of action is a growing concern. In addition to well-recognized carcinogens, various chemicals in environmental and occupational settings have been suggested to impact health, increasing susceptibility to cancer by inducing genetic and epigenetic changes. Accordingly, in this review, we have discussed recent insights into the pathological mechanisms of these chemicals, namely their effects on cell redox and calcium homeostasis, mitochondria and inflammatory signaling, with a focus on the possible implications for multi-stage carcinogenesis and its reversal by polyphenols. Plant-derived polyphenols, such as epigallocatechin-gallate, resveratrol, curcumin and anthocyanins reduce the incidence of cancer and can be useful nutraceuticals for alleviating the detrimental outcomes of harmful pollutants. However, development of therapies based on polyphenol administration requires further studies to validate the biological efficacy, identifying effective doses, mode of action and new delivery forms. Innovative microphysiological testing models are presented and specific proposals for future trials are given. Merging the current knowledge of multifactorial actions of specific polyphenols and chief environmental toxicants, this work aims to potentiate the delivery of phytochemical-based protective treatments to individuals at high-risk due to environmental exposure.
Collapse
Affiliation(s)
- Ricardo Lagoa
- School of Technology and Management, Polytechnic Institute of Leiria, Morro do Lena, Alto do Vieiro, 2411-901 Leiria, Portugal; Applied Molecular Biosciences Unit, NOVA School of Science and Technology, NOVA University of Lisbon, 2829-516 Caparica, Portugal.
| | - Dorinda Marques-da-Silva
- School of Technology and Management, Polytechnic Institute of Leiria, Morro do Lena, Alto do Vieiro, 2411-901 Leiria, Portugal; Applied Molecular Biosciences Unit, NOVA School of Science and Technology, NOVA University of Lisbon, 2829-516 Caparica, Portugal
| | - Mário Diniz
- Applied Molecular Biosciences Unit, NOVA School of Science and Technology, NOVA University of Lisbon, 2829-516 Caparica, Portugal; Department of Chemistry, NOVA School of Science and Technology, NOVA University of Lisbon, 2829-516 Caparica, Portugal
| | - Maria Daglia
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
| | - Anupam Bishayee
- Lake Erie College of Osteopathic Medicine, 5000 Lakewood Ranch Boulevard, Bradenton, FL 34211, USA
| |
Collapse
|
|
20
|
Phytochemicals and Gastrointestinal Cancer: Cellular Mechanisms and Effects to Change Cancer Progression. Biomolecules 2020; 10:biom10010105. [PMID: 31936288 PMCID: PMC7022462 DOI: 10.3390/biom10010105] [Citation(s) in RCA: 90] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Revised: 12/21/2019] [Accepted: 12/23/2019] [Indexed: 02/07/2023] Open
Abstract
Gastrointestinal (GI) cancer is a prevailing global health disease with a high incidence rate which varies by region. It is a huge economic burden on health care providers. GI cancer affects different organs in the body such as the gastric organs, colon, esophagus, intestine, and pancreas. Internal and external factors like smoking, obesity, urbanization, genetic mutations, and prevalence of Helicobacter pylori and Hepatitis B and Hepatitis C viral infections could increase the risk of GI cancer. Phytochemicals are non-nutritive bioactive secondary compounds abundantly found in fruits, grains, and vegetables. Consumption of phytochemicals may protect against chronic diseases like cardiovascular disease, neurodegenerative disease, and cancer. Multiple studies have assessed the chemoprotective effect of selected phytochemicals in GI cancer, offering support to their potential towards reducing the pathogenesis of the disease. The aim of this review was to summarize the current knowledge addressing the anti-cancerous effects of selected dietary phytochemicals on GI cancer and their molecular activities on selected mechanisms, i.e., nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), detoxification enzymes, adenosine monophosphate activated protein kinase (AMPK), wingless-related integration site/β-catenin (wingless-related integration site (Wnt) β-catenin, cell apoptosis, phosphoinositide 3-kinases (PI3K)/ protein kinase B AKT/ mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK). In this review phytochemicals were classified into four main categories: (i) carotenoids, including lutein, lycopene, and β-carotene; (ii) proanthocyanidins, including quercetin and ellagic acid; (iii) organosulfur compounds, including allicin, allyl propyl disulphide, asparagusic acid, and sulforaphane; and (iv) other phytochemicals including pectin, curcumins, p-coumaric acid and ferulic acid. Overall, phytochemicals improve cancer prognosis through the downregulation of β-catenin phosphorylation, therefore enhancing apoptosis, and upregulation of the AMPK pathway, which supports cellular homeostasis. Nevertheless, more studies are needed to provide a better understanding of the mechanism of cancer treatment using phytochemicals and possible side effects associated with this approach.
Collapse
|
|
21
|
Mudd AM, Gu T, Munagala R, Jeyabalan J, Egilmez NK, Gupta RC. Chemoprevention of Colorectal Cancer by Anthocyanidins and Mitigation of Metabolic Shifts Induced by Dysbiosis of the Gut Microbiome. Cancer Prev Res (Phila) 2019; 13:41-52. [PMID: 31796466 DOI: 10.1158/1940-6207.capr-19-0362] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Revised: 10/17/2019] [Accepted: 11/26/2019] [Indexed: 11/16/2022]
Abstract
Diets rich in fat, smoking, as well as exposure to environmental pollutants and dysbiosis of gut microbiota, increase the risk of developing colorectal cancer. Much progress has been made in combating colorectal cancer. However, options for chemoprevention from environmental insult and dysbiosis of gut microbiota remain elusive. We investigated the influence of berry-derived anthocyanidins (Anthos), with and without encapsulating them in bovine milk-derived exosomes (ExoAnthos), on the chemoprevention of bacteria-driven colon tumor development. Anthos and ExoAnthos treatment of colon cancer cells showed dose-dependent decreases in cell viability. Calculated selectivity index (SI) values for Anthos and ExoAnthos suggest that both treatments selectively targeted cancer over normal colon cells. In addition, ExoAnthos treatment yielded higher SI values than Anthos. Anthos and ExoAnthos treatment of ApcMin/+ mice inoculated with enterotoxigenic Bacteriodes fragilis (ETBF) bacteria led to significant decreases in colon tumor numbers over mice receiving vehicle treatments. Western blot analysis of normal colon, colon tumor, and liver tissue lysates showed that mice inoculated with ETBF featured increased expression of phase I enzymes in normal colon tissue and decreased expression of phase II enzymes in liver tissue. Treatment with the Anthos and ExoAnthos reverted the modulation of phase I and phase II enzymes, respectively; no significant changes in phase II enzyme expression occurred in colon tumor tissue. Treatment of HCT-116 cells with the ubiquitous carcinogen, benzo[a]pyrene (B[a]P) led to similar modulation of phase I and II enzymes, which was partially mitigated by treatment with Anthos. These results provide a promising outlook on the impact of berry Anthos for prevention and treatment of bacteria- and B[a]P-driven colorectal cancer.
Collapse
Affiliation(s)
- Ashley M Mudd
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky
| | - Tao Gu
- Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky
| | - Radha Munagala
- James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.,Department of Medicine, University of Louisville, Louisville, Kentucky
| | | | - Nejat K Egilmez
- Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky
| | - Ramesh C Gupta
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky. .,James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky
| |
Collapse
|
|
22
|
Medic N, Tramer F, Passamonti S. Anthocyanins in Colorectal Cancer Prevention. A Systematic Review of the Literature in Search of Molecular Oncotargets. Front Pharmacol 2019; 10:675. [PMID: 31281255 PMCID: PMC6597886 DOI: 10.3389/fphar.2019.00675] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 05/23/2019] [Indexed: 12/24/2022] Open
Abstract
Background: Colorectal cancer (CRC) is the malignant process that surges in the terminal part of gastrointestinal tract when adenomatous polyps convert to neoplastic cells able to infiltrate the submucosa. Despite the constant progress in applying preventive measures (screening, colonoscopy) and developing new cures (surgical and chemotherapy), CRC is still one of the leading causes of cancer death worldwide. The importance of natural dietary components in CRC prevention has been recognized. Defining the precise role of the diet and its particular molecular moieties in CRC prevention is of constant scientific interest years behind. Anthocyanins (AC), phenolic phytochemicals present in pigmented plants and vegetables, have been reported to have some role in counteracting CRC carcinogenesis. Nonetheless, evidence coming out the pre-clinical, clinical, and epidemiological studies is still controversial. This review is addressing the need to better comprehend the causes of missing data and discrepancies in investigations on the role of dietary AC in modulating CRC carcinogenesis. Methods: We have analyzed the scientific literature, available in PubMed database, according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement methodology for systematic reviews. Subsequently, two selection strategies, with their screening and eligibility criteria, were applied to retain research articles reporting in vitro and in vivo studies aimed at exploring the molecular mechanisms underlying the observed effects of AC in CRC prevention. Results: From the pool of 82 identified publications, we selected 19 articles reporting experimental or observational data on the effect of AC-enriched diets in CRC prevention in humans or murine species. Furthermore, we selected 10 articles reporting about molecular mechanisms of action of pure AC in CRC experimental models. Conclusions: The major outcome of this review is that AC showed essentially no effect in human studies, whereas AC-enriched diets proved to be effective in experimental murine models of CRC. In cell culture tests, AC showed to interfere with cell signaling pathways related to cell growth and differentiation, apoptosis, oxygen stress, and inflammation response. Further molecular characterizations are required to include AC in the panel of disease-modifying agents.
Collapse
|
|
23
|
Lagoa R, Silva J, Rodrigues JR, Bishayee A. Advances in phytochemical delivery systems for improved anticancer activity. Biotechnol Adv 2019; 38:107382. [PMID: 30978386 DOI: 10.1016/j.biotechadv.2019.04.004] [Citation(s) in RCA: 128] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 03/23/2019] [Accepted: 04/06/2019] [Indexed: 12/15/2022]
Abstract
Natural compounds have significant anticancer pharmacological activities, but often suffer from low bioavailability and selectivity that limit therapeutic use. The present work critically analyzes the latest advances on drug delivery systems designed to enhance pharmacokinetics, targeting, cellular uptake and efficacy of anticancer phytoconstituents. Various phytochemicals, including flavonoids, resveratrol, celastrol, curcumin, berberine and camptothecins, carried by liposomes, nanoparticles, nanoemulsions and films showed promising results. Strategies to avoid drug metabolism, overcome physiological barriers and achieve higher concentration at cancer sites through skin, buccal, nasal, vaginal, pulmonary and colon targeted delivery are presented. Current limitations, challenges and future research directions are also discussed.
Collapse
Affiliation(s)
- Ricardo Lagoa
- School of Technology and Management, Polytechnic Institute of Leiria, Morro do Lena, Alto do Vieiro, 2411-901 Leiria, Portugal.
| | - João Silva
- School of Technology and Management, Polytechnic Institute of Leiria, Morro do Lena, Alto do Vieiro, 2411-901 Leiria, Portugal
| | - Joaquim Rui Rodrigues
- School of Technology and Management, Polytechnic Institute of Leiria, Morro do Lena, Alto do Vieiro, 2411-901 Leiria, Portugal
| | - Anupam Bishayee
- Lake Erie College of Osteopathic Medicine, 5000 Lakewood Ranch Boulevard, Bradenton, FL 34211, USA.
| |
Collapse
|
|
24
|
Ancillotti C, Ulaszewska M, Mattivi F, Del Bubba M. Untargeted Metabolomics Analytical Strategy Based on Liquid Chromatography/Electrospray Ionization Linear Ion Trap Quadrupole/Orbitrap Mass Spectrometry for Discovering New Polyphenol Metabolites in Human Biofluids after Acute Ingestion of Vaccinium myrtillus Berry Supplement. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 2019; 30:381-402. [PMID: 30506347 DOI: 10.1007/s13361-018-2111-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 11/09/2018] [Accepted: 11/11/2018] [Indexed: 06/09/2023]
Abstract
In this work, liquid chromatography, coupled with an electrospray ionization hybrid linear ion trap quadrupole/Orbitrap mass spectrometry, has been used to accurately identify polyphenol metabolites in human serum and urine after acute ingestion of a V. myrtillus berry supplement. The supplement was obtained by cryo-milling of bilberries, which were freeze-dried within 1 week after their harvesting, to maintain the berry native composition. Thirty-six derivatives of benzoic acids, hydroxyhippuric acids, cinnamic acids, phenylpropionic acids, phenylvaleric acids, phenylpentenoic acids and abscisic acid, together with two berry-native anthocyanins, one flavonol metabolite and two catechol derivatives were putatively identified in the investigated biofluids. The annotated compounds included 13 metabolites, among glucuronides and sulphates of phenylvaleric and phenylpentenoic acids, which have been identified for the first time in human biofluids after ingestion of V. myrtillus berries. It should be emphasized that the presence of phenylvaleric and phenylpentenoic acid derivatives is in agreement with their origin from fruit native flavanol monomers and oligomers, which are widely distributed in Vaccinium berries, but usually overlooked in metabolomics studies regarding bilberry. The identification of these compounds confirmed the key-role of untargeted metabolomics approach in the discovery of new metabolites which could be biologically active. Graphical Abstract.
Collapse
Affiliation(s)
- Claudia Ancillotti
- Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Florence, Sesto Fiorentino, Italy
| | - Marynka Ulaszewska
- Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), Via Mach 1, 38010, Trento, San Michele all'Adige, Italy
| | - Fulvio Mattivi
- Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), Via Mach 1, 38010, Trento, San Michele all'Adige, Italy
- Center for Agriculture Food and Environment, University of Trento, San Michele all'Adige, Italy
| | - Massimo Del Bubba
- Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Florence, Sesto Fiorentino, Italy.
| |
Collapse
|
|
25
|
Lin Y, Li B, Zhao J, Wei L, Wang Y, Wang M, Dia VP, Meng X. Combinatorial effect of blueberry extracts and oxaliplatin in human colon cancer cells. J Cell Physiol 2019; 234:17242-17253. [DOI: 10.1002/jcp.28341] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 01/23/2019] [Accepted: 01/28/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Yang Lin
- College of Food Science Shenyang Agricultural University Shenyang Liaoning China
- Department of Food Science The University of Tennessee Institute of Agriculture Knoxville Tennessee
| | - Bin Li
- College of Food Science Shenyang Agricultural University Shenyang Liaoning China
| | - Jin Zhao
- College of Food Science Shenyang Agricultural University Shenyang Liaoning China
| | - Lulu Wei
- College of Food Science Shenyang Agricultural University Shenyang Liaoning China
| | - Yuehua Wang
- College of Food Science Shenyang Agricultural University Shenyang Liaoning China
| | - Mingyue Wang
- College of Food Science Shenyang Agricultural University Shenyang Liaoning China
| | - Vermont P. Dia
- Department of Food Science The University of Tennessee Institute of Agriculture Knoxville Tennessee
| | - Xianjun Meng
- College of Food Science Shenyang Agricultural University Shenyang Liaoning China
| |
Collapse
|
|
26
|
Caban M, Owczarek K, Chojnacka K, Lewandowska U. Overview of polyphenols and polyphenol-rich extracts as modulators of IGF-1, IGF-1R, and IGFBP expression in cancer diseases. J Funct Foods 2019. [DOI: 10.1016/j.jff.2018.11.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
|
|
27
|
Flavonoids and Colorectal Cancer Prevention. Antioxidants (Basel) 2018; 7:antiox7120187. [PMID: 30544686 PMCID: PMC6316869 DOI: 10.3390/antiox7120187] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 11/03/2018] [Accepted: 12/04/2018] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer, but despite advances in treatment, it remains the second most common cause of cancer-related mortality. Prevention may, therefore, be a key strategy in reducing colorectal cancer deaths. Given reports of an inverse association between fruit and vegetable consumption with colorectal cancer risk, there has been significant interest in understanding the metabolism and bioactivity of flavonoids, which are highly abundant in fruits and vegetables and account for their pigmentation. In this review, we discuss host and microbiota-mediated metabolism of flavonoids and the potential mechanisms by which flavonoids can exert protective effects against colon tumorigenesis, including regulation of signaling pathways involved in apoptosis, cellular proliferation, and inflammation and modulation of the gut microbiome.
Collapse
|
|
28
|
Costea T, Hudiță A, Ciolac OA, Gălățeanu B, Ginghină O, Costache M, Ganea C, Mocanu MM. Chemoprevention of Colorectal Cancer by Dietary Compounds. Int J Mol Sci 2018; 19:E3787. [PMID: 30487390 PMCID: PMC6321468 DOI: 10.3390/ijms19123787] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 11/18/2018] [Accepted: 11/23/2018] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer is one of the leading causes of death, and the third most diagnosed type of cancer, worldwide. It is most common amongst men and women over 50 years old. Risk factors include smoking, alcohol, diet, physical inactivity, genetics, alterations in gut microbiota, and associated pathologies (diabetes, obesity, chronic inflammatory bowel diseases). This review will discuss, in detail, the chemopreventive properties of some dietary compounds (phenolic compounds, carotenoids, iridoids, nitrogen compounds, organosulfur compounds, phytosterols, essential oil compounds, polyunsaturated fatty acids and dietary fiber) against colorectal cancer. We present recent data, focusing on in vitro, laboratory animals and clinical trials with the previously mentioned compounds. The chemopreventive properties of the dietary compounds involve multiple molecular and biochemical mechanisms of action, such as inhibition of cell growth, inhibition of tumor initiation, inhibition of adhesion, migration and angiogenesis, apoptosis, interaction with gut microbiota, regulation of cellular signal transduction pathways and xenobiotic metabolizing enzymes, etc. Moreover, this review will also focus on the natural dietary compounds' bioavailability, their synergistic protective effect, as well as the association with conventional therapy. Dietary natural compounds play a major role in colorectal chemoprevention and continuous research in this field is needed.
Collapse
Affiliation(s)
- Teodora Costea
- Department of Pharmacognosy, Phytochemistry and Phytotherapy, "Carol Davila" University of Medicine and Pharmacy, 020956 Bucharest, Romania.
| | - Ariana Hudiță
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania.
| | - Oana-Alina Ciolac
- Department of Biophysics, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
| | - Bianca Gălățeanu
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania.
| | - Octav Ginghină
- Department of Surgery, "Sf. Ioan" Emergency Clinical Hospital, 042122 Bucharest, Romania.
- Department II, Faculty of Dental Medicine, "Carol Davila" University of Medicine and Pharmacy, 030167 Bucharest, Romania.
| | - Marieta Costache
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania.
| | - Constanța Ganea
- Department of Biophysics, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
| | - Maria-Magdalena Mocanu
- Department of Biophysics, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
| |
Collapse
|
|
29
|
Afrin S, Giampieri F, Gasparrini M, Forbes-Hernández TY, Cianciosi D, Reboredo-Rodriguez P, Zhang J, Manna PP, Daglia M, Atanasov AG, Battino M. Dietary phytochemicals in colorectal cancer prevention and treatment: A focus on the molecular mechanisms involved. Biotechnol Adv 2018; 38:107322. [PMID: 30476540 DOI: 10.1016/j.biotechadv.2018.11.011] [Citation(s) in RCA: 117] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Revised: 11/20/2018] [Accepted: 11/20/2018] [Indexed: 12/11/2022]
Abstract
Worldwide, colorectal cancer (CRC) remains a major cancer type and leading cause of death. Unfortunately, current medical treatments are not sufficient due to lack of effective therapy, adverse side effects, chemoresistance and disease recurrence. In recent decades, epidemiologic observations have highlighted the association between the ingestion of several phytochemical-enriched foods and nutrients and the lower risk of CRC. According to preclinical studies, dietary phytochemicals exert chemopreventive effects on CRC by regulating different markers and signaling pathways; additionally, the gut microbiota plays a role as vital effector in CRC onset and progression, therefore, any dietary alterations in it may affect CRC occurrence. A high number of studies have displayed a key role of growth factors and their signaling pathways in the pathogenesis of CRC. Indeed, the efficiency of dietary phytochemicals to modulate carcinogenic processes through the alteration of different molecular targets, such as Wnt/β-catenin, PI3K/Akt/mTOR, MAPK (p38, JNK and Erk1/2), EGFR/Kras/Braf, TGF-β/Smad2/3, STAT1-STAT3, NF-кB, Nrf2 and cyclin-CDK complexes, has been proven, whereby many of these targets also represent the backbone of modern drug discovery programs. Furthermore, epigenetic analysis showed modified or reversed aberrant epigenetic changes exerted by dietary phytochemicals that led to possible CRC prevention or treatment. Therefore, our aim is to discuss the effects of some common dietary phytochemicals that might be useful in CRC as preventive or therapeutic agents. This review will provide new guidance for research, in order to identify the most studied phytochemicals, their occurrence in foods and to evaluate the therapeutic potential of dietary phytochemicals for the prevention or treatment of CRC by targeting several genes and signaling pathways, as well as epigenetic modifications. In addition, the results obtained by recent investigations aimed at improving the production of these phytochemicals in genetically modified plants have been reported. Overall, clinical data on phytochemicals against CRC are still not sufficient and therefore the preventive impacts of dietary phytochemicals on CRC development deserve further research so as to provide additional insights for human prospective studies.
Collapse
Affiliation(s)
- Sadia Afrin
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy
| | - Francesca Giampieri
- Nutrition and Food Science Group, Dept. of Analytical and Food Chemistry, CITACA, CACTI, University of Vigo, Vigo Campus, Vigo, (Spain); Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy
| | - Massimiliano Gasparrini
- Dipartimento di Scienze Agrarie, Alimentari ed Ambientali, Università Politecnica delle Marche, Ancona 60131, Italy
| | - Tamara Y Forbes-Hernández
- Nutrition and Food Science Group, Dept. of Analytical and Food Chemistry, CITACA, CACTI, University of Vigo, Vigo Campus, Vigo, (Spain)
| | - Danila Cianciosi
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy
| | - Patricia Reboredo-Rodriguez
- Nutrition and Food Science Group, Dept. of Analytical and Food Chemistry, CITACA, CACTI, University of Vigo, Vigo Campus, Vigo, (Spain)
| | - Jiaojiao Zhang
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy
| | - Piera Pia Manna
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy
| | - Maria Daglia
- Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Pavia 27100, Italy
| | - Atanas Georgiev Atanasov
- Department of Pharmacognosy, University of Vienna, Althanstrasse 14, Vienna 1090, Austria; Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Postępu 36A Street, Jastrzebiec 05-552, Poland.
| | - Maurizio Battino
- Nutrition and Food Science Group, Dept. of Analytical and Food Chemistry, CITACA, CACTI, University of Vigo, Vigo Campus, Vigo, (Spain); Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy.
| |
Collapse
|
|
30
|
Priprem A, Damrongrungruang T, Limsitthichaikoon S, Khampaenjiraroch B, Nukulkit C, Thapphasaraphong S, Limphirat W. Topical Niosome Gel Containing an Anthocyanin Complex: a Potential Oral Wound Healing in Rats. AAPS PharmSciTech 2018. [PMID: 29532424 DOI: 10.1208/s12249-018-0966-7] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Anthocyanins from dietary sources showing potential benefits as anti-inflammatory in oral lesions were developed as an anthocyanin complex (AC), comprised of extracts of Zea mays (CC) and Clitoria ternatea (CT), and formulated into a niosome gel to prove its topical oral wound healing in vitro and in vivo investigations. The AC formed nano-sized clusters of crystalline-like aggregates, occurring through both intra- and inter-molecular interactions, resulting in delivery depots of anthocyanins, following encapsulation in niosomes and incorporation into a mucoadhesive gel. In vitro permeation of anthocyanins was improved by complexation and further enhanced by encapsulation in niosomes. Collagen production in human gingival fibroblasts was promoted by AC and AC niosomes, but not CC or CT. The in vivo wound healing properties of AC gel (1 and 10%), AC niosome gel (1 and 10%), fluocinolone acetonide gel, and placebo gel were investigated for incisional wounds in the buccal cavities of Wistar rats. AC gel and AC niosome gel both reduced wound sizes after 3 days. AC niosome gel (10%) gave the highest reduction in wound sizes after day 3 (compared to fluocinolone acetonide gel, p < 0.05), and resulted in 100% wound healing by day 5. Histological observations of cross-sectioned wound tissues revealed the adverse effects of fluocinolone gel and wound healing potential of AC niosome gel. Topical application of AC niosome gel exhibited an anti-inflammatory effect and promoted oral wound closure in rats, possibly due to the improved mucosal permeability and presence of delivery depots of AC in the niosome gel.
Collapse
|
|
31
|
Lippert E, Ruemmele P, Obermeier F, Goelder S, Kunst C, Rogler G, Dunger N, Messmann H, Hartmann A, Endlicher E. Anthocyanins Prevent Colorectal Cancer Development in a Mouse Model. Digestion 2018; 95:275-280. [PMID: 28494451 DOI: 10.1159/000475524] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Accepted: 04/03/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND Colorectal cancer is the main leading cause of cancer-related deaths worldwide. Present data suggest that plant-derived anthocyanins have anti-inflammatory and chemopreventive properties. This study was aimed at evaluating the effect of an anthocyanin-rich extract from bilberries on colorectal tumour development and growth in the administration of azoxymethan (AOM)/dextran sodium sulfate (DSS) mouse model. METHODS Colonic carcinogenesis was induced by AOM and DSS 3 or 5%, respectively, in 50 female Balb/c mice. Mice received either normal food (controls) or a diet containing either 10 or 1% anthocyanin-rich bilberry extract. Colonoscopy took place at week 4 and 9 after initiation of carcinogenesis. After termination at week 9, colon samples were analysed macroscopically and microscopically. RESULTS Mice receiving 10% anthocyanins showed significantly (p < 0.004) less reduced colon length (12.1 cm [8.5-14.4 cm]) as compared to controls (11.2 cm [9.8-12.3]) indicating less inflammation. Mice fed with 10% anthocyanin-rich extract revealed significantly less mean tumour numbers (n = 1.2) compared to control (n = 14) and anthocyanin 1% treated mice (n = 10.6, p < 0.001). CONCLUSION Anthocyanins prevented the formation and growth of colorectal cancer in AOM/DSS-treated Balb/c mice. Further studies should investigate the mechanisms of how anthocyanins influence the development of colorectal cancer.
Collapse
Affiliation(s)
- Elisabeth Lippert
- Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Polyphenols in Colorectal Cancer: Current State of Knowledge including Clinical Trials and Molecular Mechanism of Action. BIOMED RESEARCH INTERNATIONAL 2018; 2018:4154185. [PMID: 29568751 PMCID: PMC5820674 DOI: 10.1155/2018/4154185] [Citation(s) in RCA: 84] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 11/08/2017] [Accepted: 12/17/2017] [Indexed: 02/08/2023]
Abstract
Polyphenols have been reported to have wide spectrum of biological activities including major impact on initiation, promotion, and progression of cancer by modulating different signalling pathways. Colorectal cancer is the second most major cause of mortality and morbidity among females and the third among males. The objective of this review is to describe the activity of a variety of polyphenols in colorectal cancer in clinical trials, preclinical studies, and primary research. The molecular mechanisms of major polyphenols related to their beneficial effects on colorectal cancer are also addressed. Synthetic modifications and other future directions towards exploiting of natural polyphenols against colorectal cancer are discussed in the last section.
Collapse
|
|
33
|
Thibado SP, Thornthwaite JT, Ballard TK, Goodman BT. Anticancer effects of Bilberry anthocyanins compared with NutraNanoSphere encapsulated Bilberry anthocyanins. Mol Clin Oncol 2017; 8:330-335. [PMID: 29399357 DOI: 10.3892/mco.2017.1520] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Accepted: 10/27/2017] [Indexed: 12/20/2022] Open
Abstract
Rapidly accumulating laboratory and clinical research evidence indicates that anthocyanins exhibit anticancer activity and the evaluation of bilberry anthocyanins as chemo-preventive agents is progressing. It has previously been demonstrated that anthocyanins upregulate tumor suppressor genes, induce apoptosis in cancer cells, repair and protect genomic DNA integrity, which is important in reducing age-associated oxidative stress, and improve neuronal and cognitive brain function. Bilberry anthocyanins have pronounced health effects, even though they have a low bioavailability. To increase the bioavailability, Bilberry was encapsulated in 5.5 nm diameter liposomal micelles, called NutraNanoSpheres (NNS), at a concentration of 2.5 mg/50 µl [25% (w/w) anthocyanins]. These Bilberry NNS were used to study the apoptotic/cytotoxic effects on K562 Human Erythroleukemic cancer cells. Flow cytometric fluorescent quantification of the uptake of propidium iodide in a special cell viability formulation into dead K562 cells was used to determine the effects of Bilberry on the viability of K562 cells. The concentrations of Bilberry that demonstrated the greatest levels of percentage inhibition, relative to the control populations, were biphasic, revealing a 60-70% inhibition between 0.018-1.14 mg/ml (n=6) and 60% inhibition at 4 mg/ml. The lowest percentage inhibition (30%) occurred at 2 mg/ml. The lethal dose 50 was determined to be 0.01-0.04 mg/ml of Bilberry per 105 K562 cells at 72 h of cell culture exposure. At 48 h incubation, the highest percentage of inhibition was only 27%, suggesting involvement of a long-term apoptotic event. These levels, which demonstrated direct cytotoxic effects, were 8-40 times lower than levels required for Bilberry that is not encapsulated. The increase in bioavailability with the Bilberry NNS and its water solubility demonstrated the feasibility of using Bilberry NNS in cancer patient clinical trials.
Collapse
Affiliation(s)
- Seth P Thibado
- Department, of Chemistry, Union University, Jackson, TN 38305, USA
| | | | - Thomas K Ballard
- Cancer Research Institute of West Tennessee, Henderson, TN 38340, USA
| | - Brandon T Goodman
- Cancer Research Institute of West Tennessee, Henderson, TN 38340, USA
| |
Collapse
|
|
34
|
Owczarek K, Lewandowska U. The Impact of Dietary Polyphenols on COX-2 Expression in Colorectal Cancer. Nutr Cancer 2017; 69:1105-1118. [PMID: 29068698 DOI: 10.1080/01635581.2017.1367940] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Polyphenols are natural compounds with high structural diversity whose common occurrence in plants renders them intrinsic dietary components. They are known to be secondary metabolites characterized by a wide spectrum of biological activities, and a growing body of evidence indicates they have anti-inflammatory potential. It is well known that inflammation plays a key role in many chronic diseases such as circulatory diseases, pulmonary diseases, autoimmune diseases, diabetes, cancer, and neurodegenerative diseases. Polyphenols influence the inflammatory process by controlling and inhibiting pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, and TNF-α, and cyclooxygenase-2 (COX-2) enzyme involved in the metabolism of arachidonic acid. Furthermore, polyphenols exhibit anti-inflammatory activity on many levels via NF-κB inhibition, and MAPK, iNOS, and growth factors regulation. This paper reviews the current state of knowledge concerning the potential of various dietary polyphenols to inhibit the effects of COX-2 in colon cancer, by examining the available evidence regarding the efficacy and safety of these compounds obtained from in vitro and animal studies.
Collapse
Affiliation(s)
- Katarzyna Owczarek
- a Department of Biochemistry , Faculty of Medicine, Medical University of Lodz , Lodz , Poland
| | - Urszula Lewandowska
- a Department of Biochemistry , Faculty of Medicine, Medical University of Lodz , Lodz , Poland
| |
Collapse
|
|
35
|
de Sousa Moraes LF, Sun X, Peluzio MDCG, Zhu MJ. Anthocyanins/anthocyanidins and colorectal cancer: What is behind the scenes? Crit Rev Food Sci Nutr 2017; 59:59-71. [PMID: 28799785 DOI: 10.1080/10408398.2017.1357533] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Colorectal cancer (CRC) is one of the most common cause of cancer death. Phytochemicals, especially anthocyanins/anthocyanidins (A/A), have gathered attention of the scientific community owing to their anti-inflammatory, antioxidant, and cancer-inhibitory properties. In this review, we discussed the possible mechanisms whereby A/A exhibit intestinal anticarcinogenic characteristics. Anthocyanins/anthocyanidins inhibit the pro-inflammatory NF-κB pathway, attenuate Wnt signaling and suppress abnormal epithelial cell proliferation. In addition, A/A induce mitochondrial-mediated apoptosis and downregulate Akt/mTOR (mammalian target of rapamycin) pathway. Furthermore, activation of AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) also contributes to the anti-carcinogenic effects of A/A. Finally, downregulation of metalloproteinases (MMPs) by A/A inhibits tumor invasion and metastasis. In conclusion, A/A exert their anti-tumor effects against colorectal carcinogenesis via multiple mechanisms, providing insights into the use of A/A as a natural chemopreventive intervention on major colorectal carcinogenesis.
Collapse
Affiliation(s)
- Luís Fernando de Sousa Moraes
- a School of Food Science , Washington State University , Pullman , WA , USA.,b Department of Nutrition and Health , Universidade Federal de Viçosa , Viçosa - Minas Gerais , Brazil
| | - Xiaofei Sun
- a School of Food Science , Washington State University , Pullman , WA , USA
| | | | - Mei-Jun Zhu
- a School of Food Science , Washington State University , Pullman , WA , USA
| |
Collapse
|
|
36
|
Asadi K, Ferguson LR, Philpott M, Karunasinghe N. Cancer-preventive Properties of an Anthocyanin-enriched Sweet Potato in the APC MIN Mouse Model. J Cancer Prev 2017; 22:135-146. [PMID: 29018778 PMCID: PMC5624454 DOI: 10.15430/jcp.2017.22.3.135] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 09/01/2017] [Accepted: 09/03/2017] [Indexed: 12/11/2022] Open
Abstract
Background Anthocyanin-rich foods and preparations have been reported to reduce the risk of life-style related diseases, including cancer. The SL222 sweet potato, a purple-fleshed cultivar developed in New Zealand, accumulates high levels of anthocyanins in its storage root. Methods We examined the chemopreventative properties of the SL222 sweet potato in the C57BL/6J-APCMIN/+ (APCMIN) mouse, a genetic model of colorectal cancer. APCMIN and C57BL/6J wild-type mice (n=160) were divided into four feeding groups consuming diets containing 10% SL222 sweet potato flesh, 10% SL222 sweet potato skin, or 0.12% ARE (Anthocyanin rich-extract prepared from SL222 sweet potato at a concentration equivalent to the flesh-supplemented diet) or a control diet (AIN-76A) for 18 weeks. At 120 days of age, the mice were anaesthetised, and blood samples were collected before the mice were sacrificed. The intestines were used for adenoma enumeration. Results The SL222 sweet potato-supplemented diets reduced the adenoma number in the APCMIN mice. Conclusions These data have significant implications for the use of this sweet potato variant in protection against colorectal cancer.
Collapse
Affiliation(s)
- Khalid Asadi
- Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Lynnette R Ferguson
- Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.,Discipline of Nutrition and Dietetics, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Martin Philpott
- Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Nishi Karunasinghe
- Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| |
Collapse
|
|
37
|
Singh AN, Baruah MM, Sharma N. Structure Based docking studies towards exploring potential anti-androgen activity of selected phytochemicals against Prostate Cancer. Sci Rep 2017; 7:1955. [PMID: 28512306 PMCID: PMC5434041 DOI: 10.1038/s41598-017-02023-5] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Accepted: 04/04/2017] [Indexed: 01/07/2023] Open
Abstract
Prostate cancer (PCa) is the second most common malignancy amongst men worldwide. Under PCa maintenance therapy drugs acting as antagonists/partial agonists of hormone receptors against the prostate tissue are used in clinical practices. Prominent drugs being Cyproterone acetate, Flutamide, Bicalutamide, they not only cause acute and long-term toxicity, but also develops drug resistance among patients. Our focus has been on phytochemicals which do not exhibit any cytotoxicity and have significant androgen receptor (AR) inhibition activity. As Protein- Ligand interactions play a key role in structure based drug design, so by using molecular docking, we screened 803 phytochemicals and investigated their binding affinity against AR. The three dimensional (3D) structure of AR was retrieved from Protein Data Bank, and docked with 3D Pubchem structures of 803 phytochemicals using Argus Lab. Molecular docking and drug likeness studies were made using ADMET properties while Lipinski's rule of five was performed for the phytochemicals to evaluate their anti-prostate cancer activity. The results showed that Isobavachin exhibited best binding affinity of -13.73 kcal/mol with AR followed by Glabranin, Anthocyanin and Eriosemation. Our studies therefore reveal that these four phytochemicals could be promising candidates for further evaluation for PCa prevention or management.
Collapse
Affiliation(s)
- Anshika N Singh
- Symbiosis School of Biological Sciences, Symbiosis International University, Gram- Lavale; Taluka - Mulshi, Pune, India
| | - Meghna M Baruah
- Symbiosis School of Biological Sciences, Symbiosis International University, Gram- Lavale; Taluka - Mulshi, Pune, India
| | - Neeti Sharma
- Symbiosis School of Biological Sciences, Symbiosis International University, Gram- Lavale; Taluka - Mulshi, Pune, India.
| |
Collapse
|
|
38
|
Majewska M, Lewandowska U. The chemopreventive and anticancer potential against colorectal cancer of polyphenol-rich fruit extracts. FOOD REVIEWS INTERNATIONAL 2017. [DOI: 10.1080/87559129.2017.1307388] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
|
|
39
|
Bishayee A, Haskell Y, Do C, Siveen KS, Mohandas N, Sethi G, Stoner GD. Potential Benefits of Edible Berries in the Management of Aerodigestive and Gastrointestinal Tract Cancers: Preclinical and Clinical Evidence. Crit Rev Food Sci Nutr 2017; 56:1753-75. [PMID: 25781639 DOI: 10.1080/10408398.2014.982243] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Epidemiological reports as well as experimental studies have demonstrated the significant health benefits provided by regular berry consumption. Berries possess both prophylactic and therapeutic potential against several chronic illnesses, such as cardiovascular, neurodegenerative, and neoplastic diseases. Berries owe their health benefits to phytoconstituents, such as polyphenolic anthocyanins, ellagic acid, and a diverse array of phytochemicals bestowed with potent antioxidant and anti-inflammatory effects as well as the ability to engage a multitude of signaling pathways. This review highlights the principal chemical constituents present in berries and their primary molecular targets. The article presents and critically analyzes the chemopreventive and therapeutic potential of berry extracts, fractions, and bioactive components on various cancers of the gastrointestinal tract (GIT), including esophageal, stomach, intestinal, and colorectal cancers as well as cancers of the upper aerodigestive tract, such as oral cancer. The current status of clinical studies evaluating berry products in several aforementioned cancers is presented. Various emerging issues including dose-ranging and dosage forms, the role of synergy and the usage of combination therapy as well as other relevant areas essential for the development of berry phytoconstituents as mainstream chemopreventive and therapeutic agents against aerodigestive and GIT cancers are critically discussed.
Collapse
Affiliation(s)
- Anupam Bishayee
- a Department of Pharmaceutical Sciences , College of Pharmacy, Larkin Health Sciences Institute , Miami , Florida USA
| | - Yennie Haskell
- b Department of Pharmaceutical Sciences , College of Pharmacy, Northeast Ohio Medical University , Rootstown , Ohio USA
| | - Chau Do
- b Department of Pharmaceutical Sciences , College of Pharmacy, Northeast Ohio Medical University , Rootstown , Ohio USA
| | - Kodappully Sivaraman Siveen
- c Department of Pharmacology , Yong Loo Lin School of Medicine, National University of Singapore , Singapore
| | - Nima Mohandas
- d School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University , Western Australia , Australia
| | - Gautam Sethi
- c Department of Pharmacology , Yong Loo Lin School of Medicine, National University of Singapore , Singapore.,d School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University , Western Australia , Australia
| | - Gary D Stoner
- e Division of Hematology and Oncology , Department of Medicine, Medical College of Wisconsin , Milwaukee , Wisconsin USA
| |
Collapse
|
|
40
|
Kangawa Y, Yoshida T, Maruyama K, Okamoto M, Kihara T, Nakamura M, Ochiai M, Hippo Y, Hayashi SM, Shibutani M. Cilostazol and enzymatically modified isoquercitrin attenuate experimental colitis and colon cancer in mice by inhibiting cell proliferation and inflammation. Food Chem Toxicol 2017; 100:103-114. [DOI: 10.1016/j.fct.2016.12.018] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Revised: 12/04/2016] [Accepted: 12/14/2016] [Indexed: 12/26/2022]
|
|
41
|
Kristo AS, Klimis-Zacas D, Sikalidis AK. Protective Role of Dietary Berries in Cancer. Antioxidants (Basel) 2016; 5:antiox5040037. [PMID: 27775562 PMCID: PMC5187535 DOI: 10.3390/antiox5040037] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 09/24/2016] [Accepted: 10/11/2016] [Indexed: 12/25/2022] Open
Abstract
Dietary patterns, including regular consumption of particular foods such as berries as well as bioactive compounds, may confer specific molecular and cellular protection in addition to the overall epidemiologically observed benefits of plant food consumption (lower rates of obesity and chronic disease risk), further enhancing health. Mounting evidence reports a variety of health benefits of berry fruits that are usually attributed to their non-nutritive bioactive compounds, mainly phenolic substances such as flavonoids or anthocyanins. Although it is still unclear which particular constituents are responsible for the extended health benefits, it appears that whole berry consumption generally confers some anti-oxidant and anti-inflammatory protection to humans and animals. With regards to cancer, studies have reported beneficial effects of berries or their constituents including attenuation of inflammation, inhibition of angiogenesis, protection from DNA damage, as well as effects on apoptosis or proliferation rates of malignant cells. Berries extend effects on the proliferation rates of both premalignant and malignant cells. Their effect on premalignant cells is important for their ability to cause premalignant lesions to regress both in animals and in humans. The present review focuses primarily on in vivo and human dietary studies of various berry fruits and discusses whether regular dietary intake of berries can prevent cancer initiation and delay progression in humans or ameliorate patients’ cancer status.
Collapse
Affiliation(s)
- Aleksandra S Kristo
- Department of Nutrition and Dietetics, Istanbul Yeni Yuzyil University, Yilanli Ayasma Caddesi No. 26, Istanbul 34010, Turkey.
| | | | - Angelos K Sikalidis
- Department of Nutrition and Dietetics, Istanbul Yeni Yuzyil University, Yilanli Ayasma Caddesi No. 26, Istanbul 34010, Turkey.
| |
Collapse
|
|
42
|
Singh CK, Siddiqui IA, El-Abd S, Mukhtar H, Ahmad N. Combination chemoprevention with grape antioxidants. Mol Nutr Food Res 2016; 60:1406-15. [PMID: 26829056 DOI: 10.1002/mnfr.201500945] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2015] [Revised: 01/14/2016] [Accepted: 01/17/2016] [Indexed: 12/29/2022]
Abstract
Antioxidant ingredients present in grape have been extensively investigated for their cancer chemopreventive effects. However, much of the work has been done on individual ingredients, especially focusing on resveratrol and quercetin. Phytochemically, whole grape represents a combination of numerous phytonutrients. Limited research has been done on the possible synergistic/additive/antagonistic interactions among the grape constituents. Among these phytochemical constituents of grapes, resveratrol, quercetin, kaempferol, catechin, epicatechin, and anthocyanins (cyanidin and malvidin) constitute more than 70% of the grape polyphenols. Therefore, these have been relatively well studied for their chemopreventive effects against a variety of cancers. While a wealth of information is available individually on cancer chemopreventive/anti-proliferative effects of resveratrol and quercetin, limited information is available regarding the other major constituents of grape. Studies have also suggested that multiple grape antioxidants, when used in combination, alone or with other agents/drugs show synergistic or additive anti-proliferative response. Based on strong rationale emanating from published studies, it seems probable that a combination of multiple grape ingredients alone or together with other agents could impart 'additive synergism' against cancer.
Collapse
Affiliation(s)
- Chandra K Singh
- Department of Dermatology, University of Wisconsin, Madison, WI, USA
| | - Imtiaz A Siddiqui
- Department of Dermatology, University of Wisconsin, Madison, WI, USA
| | - Sabah El-Abd
- Department of Dermatology, University of Wisconsin, Madison, WI, USA
| | - Hasan Mukhtar
- Department of Dermatology, University of Wisconsin, Madison, WI, USA
| | - Nihal Ahmad
- Department of Dermatology, University of Wisconsin, Madison, WI, USA
| |
Collapse
|
|
43
|
Charepalli V, Reddivari L, Vadde R, Walia S, Radhakrishnan S, Vanamala JKP. Eugenia jambolana (Java Plum) Fruit Extract Exhibits Anti-Cancer Activity against Early Stage Human HCT-116 Colon Cancer Cells and Colon Cancer Stem Cells. Cancers (Basel) 2016; 8:cancers8030029. [PMID: 26927179 PMCID: PMC4810113 DOI: 10.3390/cancers8030029] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Revised: 02/20/2016] [Accepted: 02/22/2016] [Indexed: 12/20/2022] Open
Abstract
The World Health Organization predicts over a 70% increase in cancer incidents in developing nations over the next decade. Although these nations have limited access to novel therapeutics, they do have access to foods that contain chemopreventive bioactive compounds such as anthocyanins, and as such, consumption of these foods can be encouraged to combat cancer. We and others have previously characterized the anti-colon cancer properties of dietary anthocyanins from different sources. Eugenia jambolana (Java plum) is a tropical medicinal fruit rich in anthocyanins, however, its anti-colon cancer properties are not well characterized. Furthermore, recent evidence suggests that colon cancer stem cells (colon CSCs) promote resistance to chemotherapy, relapse of tumors and contribute to poor prognosis. The objectives of this study were to 1) characterize the anthocyanin profile of Java plum using HPLC-MS; and 2) determine the anti-proliferative (cell counting and MTT) and pro-apoptotic (TUNEL and caspase 3/7 glo assay) properties of Java plum fruit extract (JPE) using HCT-116 colon cancer cell line and colon CSCs (positive for CD 44, CD 133 and ALDH1b1 markers). HPLC-MS analysis showed that JPE contains a variety of anthocyanins including glucosides of delphinidin, cyanidin, petunidin, peonidin and malvidin. JPE anthocyanins suppressed (p < 0.05) proliferation in HCT-116 cells and elevated (p < 0.05) apoptosis in both HCT-116 cells and colon CSCs. JPE also suppressed the stemness in colon CSCs as evaluated using colony formation assay. These results warrant further assessment of the anti-cancer activity of JPE, and its molecular mechanisms using pre-clinical models of colon cancer.
Collapse
Affiliation(s)
- Venkata Charepalli
- Departmetn of Food Science, The Pennsylvania State University, University Park, PA 16802, USA.
| | - Lavanya Reddivari
- Departmetn of Plant Science, The Pennsylvania State University, University Park, PA 16802, USA.
| | - Ramakrishna Vadde
- Departmetn of Food Science, The Pennsylvania State University, University Park, PA 16802, USA.
| | - Suresh Walia
- Division of Agricultural Chemicals, Indian Agricultural Research Institute, New Delhi 110001, India.
| | - Sridhar Radhakrishnan
- Departmetn of Food Science, The Pennsylvania State University, University Park, PA 16802, USA.
| | - Jairam K P Vanamala
- Departmetn of Food Science, The Pennsylvania State University, University Park, PA 16802, USA.
- The Pennsylvania State Hershey Cancer Institute, Penn State Milton S Hershey Medical Center, Hershey, PA 16802, USA.
| |
Collapse
|
|
44
|
Vrzal R. Anthocyanidins but not anthocyanins inhibit P-glycoprotein-mediated calcein extrusion - possible implication for orally administered drugs. Fundam Clin Pharmacol 2016; 30:248-52. [DOI: 10.1111/fcp.12183] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Revised: 12/29/2015] [Accepted: 01/25/2016] [Indexed: 01/08/2023]
Affiliation(s)
- Radim Vrzal
- Department of Cell Biology and Genetics; Faculty of Science; Palacky University; Slechtitelu 27 783 71 Olomouc Czech Republic
| |
Collapse
|
|
45
|
Afrin S, Giampieri F, Gasparrini M, Forbes-Hernandez TY, Varela-López A, Quiles JL, Mezzetti B, Battino M. Chemopreventive and Therapeutic Effects of Edible Berries: A Focus on Colon Cancer Prevention and Treatment. Molecules 2016; 21:169. [PMID: 26840292 PMCID: PMC6273426 DOI: 10.3390/molecules21020169] [Citation(s) in RCA: 97] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2015] [Revised: 01/22/2016] [Accepted: 01/26/2016] [Indexed: 12/15/2022] Open
Abstract
Colon cancer is one of the most prevalent diseases across the world. Numerous epidemiological studies indicate that diets rich in fruit, such as berries, provide significant health benefits against several types of cancer, including colon cancer. The anticancer activities of berries are attributed to their high content of phytochemicals and to their relevant antioxidant properties. In vitro and in vivo studies have demonstrated that berries and their bioactive components exert therapeutic and preventive effects against colon cancer by the suppression of inflammation, oxidative stress, proliferation and angiogenesis, through the modulation of multiple signaling pathways such as NF-κB, Wnt/β-catenin, PI3K/AKT/PKB/mTOR, and ERK/MAPK. Based on the exciting outcomes of preclinical studies, a few berries have advanced to the clinical phase. A limited number of human studies have shown that consumption of berries can prevent colorectal cancer, especially in patients at high risk (familial adenopolyposis or aberrant crypt foci, and inflammatory bowel diseases). In this review, we aim to highlight the findings of berries and their bioactive compounds in colon cancer from in vitro and in vivo studies, both on animals and humans. Thus, this review could be a useful step towards the next phase of berry research in colon cancer.
Collapse
Affiliation(s)
- Sadia Afrin
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy.
| | - Francesca Giampieri
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy.
| | - Massimiliano Gasparrini
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy.
| | - Tamara Y Forbes-Hernandez
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy.
| | - Alfonso Varela-López
- Department of Physiology, Institute of Nutrition and Food Technology ''José Mataix", Biomedical Research Centre, University of Granada, Armilla, Avda. del Conocimiento s.n., Armilla 18100, Spain.
| | - José L Quiles
- Department of Physiology, Institute of Nutrition and Food Technology ''José Mataix", Biomedical Research Centre, University of Granada, Armilla, Avda. del Conocimiento s.n., Armilla 18100, Spain.
| | - Bruno Mezzetti
- Dipartimento di Scienze Agrarie, Alimentari e Ambientali, Università Politecnica delle Marche, Via Ranieri 65, Ancona 60131, Italy.
| | - Maurizio Battino
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy.
- Centre for Nutrition & Health, Universidad Europea del Atlantico (UEA), Santander 39011, Spain.
| |
Collapse
|
|
46
|
Park MY, Kim JM, Kim JS, Choung MG, Sung MK. Chemopreventive Action of Anthocyanin-rich Black Soybean Fraction in APC (Min/+) Intestinal Polyposis Model. J Cancer Prev 2015; 20:193-201. [PMID: 26473158 PMCID: PMC4597808 DOI: 10.15430/jcp.2015.20.3.193] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Anthocyanins have been shown to inhibit cancer cell growth by suppressing oxidative stress and inflammatory responses. The purpose of this study was to investigate the effects of an anthocyanin-rich extract (AE) from black soybean coat on intestinal carcinogenesis. METHODS Apc (Min/+) mice were fed a diet of 0.2% or 0.5% AE for 7 weeks. We analyzed the number of intestinal tumors, oxidative stress and inflammatory markers associated with β-catenin and cytosolic phospholipase A2 (cPLA2) signals. The number of intestinal tumors, and cellular expression of β-catenin were determined. RESULTS The number of intestinal tumors was significantly lower in mice fed a 0.5% AE diet compared to those of the other groups. Cytosolic β-catenin expression was significantly decreased in the AE supplemented groups compared to that of the control animals. In addition, mucosa expression of cyclooxygenase-2 and cPLA2 were also significantly decreased in the 0.5% AE group, by 32% and 62%, respectively, compared to the control group. CONCLUSIONS These results suggest that dietary AE reduced the development of intestinal tumors, possibly through the ability to suppress oxidative stresses, decreasing inflammatory responses mediated by β-catenin associated signals.
Collapse
Affiliation(s)
- Mi-Young Park
- Department of Food and Nutrition Education, Graduate School of Education, Soonchunhyang University, Asan, Korea
| | - Jung-Mi Kim
- Department of Food and Nutrition Education, Graduate School of Education, Soonchunhyang University, Asan, Korea
| | - Jong-Sang Kim
- Department of Food and Nutrition Education, Graduate School of Education, Soonchunhyang University, Asan, Korea
| | - Myoung-Gun Choung
- Department of Food and Nutrition Education, Graduate School of Education, Soonchunhyang University, Asan, Korea
| | - Mi-Kyung Sung
- Department of Food and Nutrition Education, Graduate School of Education, Soonchunhyang University, Asan, Korea
| |
Collapse
|
|
47
|
Núñez-Sánchez MA, González-Sarrías A, Romo-Vaquero M, García-Villalba R, Selma MV, Tomás-Barberán FA, García-Conesa MT, Espín JC. Dietary phenolics against colorectal cancer--From promising preclinical results to poor translation into clinical trials: Pitfalls and future needs. Mol Nutr Food Res 2015; 59:1274-91. [PMID: 25693744 DOI: 10.1002/mnfr.201400866] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Revised: 02/10/2015] [Accepted: 02/11/2015] [Indexed: 01/09/2023]
Abstract
Colorectal cancer (CRC) remains a major cause of cancer death worldwide. Over 70% of CRC cases are sporadic and related to lifestyle. Epidemiological studies inversely correlate CRC incidence with the intake of fruits and vegetables but not with their phenolic content. Preclinical studies using in vitro (cell lines) and animal models of CRC have reported anticancer effects for dietary phenolics through the regulation of different markers and signaling pathways. Herein, we review and contrast the evidence between preclinical studies and clinical trials (patients with CRC or at risk, familial adenopolyposis or aberrant crypt foci) investigating the protective effects of curcumin, resveratrol, isoflavones, green tea extracts (epigallocatechin gallate), black raspberry powder (anthocyanins and ellagitannins), bilberry extract (anthocyanins), ginger extracts (gingerol derivatives), and pomegranate extracts (ellagitannins and ellagic acid). To date, curcumin is the most promising polyphenol as possible future adjuvant in CRC management. Overall, the clinical evidence of dietary phenolics against CRC is still weak and the amounts needed to exert some effects largely exceed common dietary doses. We discuss here the possible reasons behind the gap between preclinical and clinical research (inconsistence of results, lack of clinical endpoints, etc.), and provide an outlook and a roadmap to approach this topic.
Collapse
Affiliation(s)
- María A Núñez-Sánchez
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - Antonio González-Sarrías
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - María Romo-Vaquero
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - Rocío García-Villalba
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - María V Selma
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - Francisco A Tomás-Barberán
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - María-Teresa García-Conesa
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - Juan Carlos Espín
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| |
Collapse
|
|
48
|
Carvalho FB, Gutierres JM, Bohnert C, Zago AM, Abdalla FH, Vieira JM, Palma HE, Oliveira SM, Spanevello RM, Duarte MM, Lopes ST, Aiello G, Amaral MG, Pippi NL, Andrade CM. Anthocyanins suppress the secretion of proinflammatory mediators and oxidative stress, and restore ion pump activities in demyelination. J Nutr Biochem 2015; 26:378-90. [DOI: 10.1016/j.jnutbio.2014.11.006] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Revised: 10/09/2014] [Accepted: 11/13/2014] [Indexed: 12/23/2022]
|
|
49
|
Miura K, Satoh M, Kinouchi M, Yamamoto K, Hasegawa Y, Kakugawa Y, Kawai M, Uchimi K, Aizawa H, Ohnuma S, Kajiwara T, Sakurai H, Fujiya T. The use of natural products in colorectal cancer drug discovery. Expert Opin Drug Discov 2015; 10:411-26. [DOI: 10.1517/17460441.2015.1018174] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- Koh Miura
- 1Miyagi Cancer Center, Department of Surgery, 47-1 Nodayama, Natori 981-1293, Japan ;
| | - Masayuki Satoh
- 2Miyagi Cancer Center, Department of Surgery, 47-1 Nodayama, Natori 981-1293, Japan
| | - Makoto Kinouchi
- 2Miyagi Cancer Center, Department of Surgery, 47-1 Nodayama, Natori 981-1293, Japan
| | - Kuniharu Yamamoto
- 2Miyagi Cancer Center, Department of Surgery, 47-1 Nodayama, Natori 981-1293, Japan
| | - Yasuhiro Hasegawa
- 2Miyagi Cancer Center, Department of Surgery, 47-1 Nodayama, Natori 981-1293, Japan
| | - Yoichiro Kakugawa
- 2Miyagi Cancer Center, Department of Surgery, 47-1 Nodayama, Natori 981-1293, Japan
| | - Masaaki Kawai
- 2Miyagi Cancer Center, Department of Surgery, 47-1 Nodayama, Natori 981-1293, Japan
| | - Kiyoshi Uchimi
- 3Miyagi Cancer Center, Department of Gastroenterology, 47-1 Nodayama, Natori 981-1293, Japan
| | - Hiroki Aizawa
- 3Miyagi Cancer Center, Department of Gastroenterology, 47-1 Nodayama, Natori 981-1293, Japan
| | - Shinobu Ohnuma
- 4Tohoku University Graduate School of Medicine, Department of Surgery, 1-1 Seiryo-machi, Sendai 980-8574, Japan
| | - Taiki Kajiwara
- 4Tohoku University Graduate School of Medicine, Department of Surgery, 1-1 Seiryo-machi, Sendai 980-8574, Japan
| | - Hiroto Sakurai
- 2Miyagi Cancer Center, Department of Surgery, 47-1 Nodayama, Natori 981-1293, Japan
| | - Tsuneaki Fujiya
- 2Miyagi Cancer Center, Department of Surgery, 47-1 Nodayama, Natori 981-1293, Japan
| |
Collapse
|
|
50
|
Jaganathan SK, Vellayappan MV, Narasimhan G, Supriyanto E, Octorina Dewi DE, Narayanan ALT, Balaji A, Subramanian AP, Yusof M. Chemopreventive effect of apple and berry fruits against colon cancer. World J Gastroenterol 2014; 20:17029-17036. [PMID: 25493015 PMCID: PMC4258571 DOI: 10.3748/wjg.v20.i45.17029] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Revised: 06/16/2014] [Accepted: 08/28/2014] [Indexed: 02/07/2023] Open
Abstract
Colon cancer arises due to the conversion of precancerous polyps (benign) found in the inner lining of the colon. Prevention is better than cure, and this is very true with respect to colon cancer. Various epidemiologic studies have linked colorectal cancer with food intake. Apple and berry juices are widely consumed among various ethnicities because of their nutritious values. In this review article, chemopreventive effects of these fruit juices against colon cancer are discussed. Studies dealing with bioavailability, in vitro and in vivo effects of apple and berry juices are emphasized in this article. A thorough literature survey indicated that various phenolic phytochemicals present in these fruit juices have the innate potential to inhibit colon cancer cell lines. This review proposes the need for more preclinical evidence for the effects of fruit juices against different colon cancer cells, and also strives to facilitate clinical studies using these juices in humans in large trials. The conclusion of the review is that these apple and berry juices will be possible candidates in the campaign against colon cancer.
Collapse
|