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Górska-Jakubowska S, Wu Y, Turło J, Xu B. Critical Review on the Anti-Tumor Activity of Bioactive Compounds from Edible and Medicinal Mushrooms over the Last Five Years. Nutrients 2025; 17:1887. [PMID: 40507156 PMCID: PMC12157108 DOI: 10.3390/nu17111887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2025] [Revised: 05/27/2025] [Accepted: 05/29/2025] [Indexed: 06/16/2025] Open
Abstract
In recent years, the incidence rate of cancer has been on the rise all over the world, and the age of cancer patients has shown a younger trend, which seriously endangers patients' health. Edible/medicinal mushrooms have not only become a new source of nutritional supplements but have also emerged as a promising adjunct to conventional medicine, either by directly or indirectly killing tumor cells and enhancing immunity, or through their use in conjunction with modern cancer therapies to enhance their efficacy or reduce their side-effects, improving patients' quality of life. Although the anti-cancer potential of edible and medicinal mushrooms has been widely studied in the past, this review focuses on the most recent literature from the last five years, providing an up-to-date and comprehensive summary of the current findings. In this review, we aim to analyze the anti-cancer effects of edible/medicinal mushrooms, including Schizophyllum commune, Trametes versicolor, Grifola frondosa, Ganoderma lucidum, Lentinula edodes, Laetiporus sulphureus, Boletus edulis, and Phellinus igniarius, as well as their potential anti-cancer mechanisms, providing strong theoretical support for the further development of edible/medicinal mushroom anti-cancer products.
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Affiliation(s)
- Sandra Górska-Jakubowska
- Department of Drug Technology and Pharmaceutical Biotechnology, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland; (S.G.-J.); (J.T.)
| | - Yingzi Wu
- Food Science and Technology Program, Department of Life Sciences, Beijing Normal-Hong Kong Baptist University, Zhuhai 519087, China;
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Jadwiga Turło
- Department of Drug Technology and Pharmaceutical Biotechnology, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland; (S.G.-J.); (J.T.)
| | - Baojun Xu
- Food Science and Technology Program, Department of Life Sciences, Beijing Normal-Hong Kong Baptist University, Zhuhai 519087, China;
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Han S, Luo Y, Hu Z, Li X, Zhou Y, Luo F. Tumor Microenvironment Targeted by Polysaccharides in Cancer Prevention: Expanding Roles of Gut Microbiota and Metabolites. Mol Nutr Food Res 2025; 69:e202400750. [PMID: 39757562 DOI: 10.1002/mnfr.202400750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 10/31/2024] [Accepted: 12/02/2024] [Indexed: 01/07/2025]
Abstract
Since the development of immune checkpoint inhibitors (ICIs), immunotherapy has been widely used as a novel cancer treatment. However, the efficacy of tumor immunotherapy is largely dependent on the tumor microenvironment (TME). The high degree of heterogeneity within TME remains a major obstacle to acquire satisfactory therapeutic. Emerging studies suggest that gut microbiota is becoming an important regulator of TME. Polysaccharides as tumor immunotherapeutic agents or immune adjuvants not only exhibit antitumor activity by targeting gut microbiota, but also expand their role in the tumor immunotherapy by remodeling TME. To date, the mechanism by which polysaccharides targeting TME for tumor prevention via gut microbiota has not been deeply investigated. In this review, recent advances in the regulation of TME by polysaccharides through gut microbiota were systematically outlined, and the challenges and possible solutions in the clinical application of TME-targeted polysaccharides were discussed. Exploring the relationship between polysaccharides and TME from the perspective of gut microbiota may provide new ideas for the application of polysaccharides in tumor immunotherapy. This is a new area with major challenges that deserve further exploration.
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Affiliation(s)
- Shuai Han
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha, Hunan, China
- College of Tea and Food, Wuyi University, Wuyishan, Fujian, China
| | - Yi Luo
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zuomin Hu
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha, Hunan, China
| | - Xinhua Li
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yaping Zhou
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha, Hunan, China
| | - Feijun Luo
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha, Hunan, China
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Jędrzejewski T, Sobocińska J, Maciejewski B, Spisz P, Walczak-Skierska J, Pomastowski P, Wrotek S. In vitro treatment of triple-negative breast cancer cells with an extract from the Coriolus versicolor mushroom changes macrophage properties related to tumourigenesis. Immunol Res 2024; 73:14. [PMID: 39680299 DOI: 10.1007/s12026-024-09574-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 10/21/2024] [Indexed: 12/17/2024]
Abstract
Macrophages, the most abundant cells that participate in tumour progression, are the subject of a number of anticancer therapy approaches. Our previous results revealed that an extract of the fungus Coriolus versicolor (CV) has anti-cancer and immunomodulatory properties. The aim of the present study was to investigate whether CV extract-treated triple-negative breast cancer (TNBC) cells can release factors that can reprogram macrophages from pro-tumourigenic to anti-cancer subtypes. RAW 264.7 macrophages were cultured in a conditioned medium (CM) from non-treated 4T1 breast cancer cells (CM-NT) or CV extract-stimulated cells (CM-CV). After treatment, the following macrophage properties were evaluated: cell viability; M1/M2 phenotype (enzyme activities: iNOS and arginase 1; and expression of CD molecules: CD80 and CD163); cytokine concentrations: IL-6, TNF-α, IL-10, TGF-β, MCP-1 and VEGF; migration level; and ROS production. The results revealed that, compared with normal cells, TNBC cells stimulated with CV extract create a microenvironment that promotes a decrease in macrophage viability and migration, intracellular ROS production, and pro-angiogenic cytokine production (VEGF and MCP-1). Moreover, CM-CV decreased the expression of M2 macrophage markers (arginase 1 and CD163; IL-10 and TGF-β) but upregulated the expression of M1 cell markers (iNOS and CD80; IL-6 and TNF-α). We concluded that CV extract modifies the tumour microenvironment and changes macrophage polarisation toward functioning as an anti-tumour agent. Therefore, it is promising to use in the treatment of TNBC-associated macrophages.
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Affiliation(s)
- Tomasz Jędrzejewski
- Department of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Lwowska 1 Street, 87-100, Toruń, Poland.
| | - Justyna Sobocińska
- Department of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Lwowska 1 Street, 87-100, Toruń, Poland
| | - Bartosz Maciejewski
- Department of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Lwowska 1 Street, 87-100, Toruń, Poland
| | - Paulina Spisz
- Department of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Lwowska 1 Street, 87-100, Toruń, Poland
| | - Justyna Walczak-Skierska
- Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University in Toruń, Wileńska 4 Street, 87-100, Toruń, Poland
| | - Paweł Pomastowski
- Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University in Toruń, Wileńska 4 Street, 87-100, Toruń, Poland
- Department of Inorganic and Coordination Chemistry, Nicolaus Copernicus University in Toruń, Gagarina 7 Street, 87-100, Toruń, Poland
| | - Sylwia Wrotek
- Department of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Lwowska 1 Street, 87-100, Toruń, Poland
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Wang XY, Chen AQ, Huang J, Luo JH, Zou Q. A review on structure, bioactivity, mechanism, structure-activity relationship and application of anti-breast cancer polysaccharides. Int J Biol Macromol 2024; 282:137043. [PMID: 39476909 DOI: 10.1016/j.ijbiomac.2024.137043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 10/01/2024] [Accepted: 10/27/2024] [Indexed: 11/05/2024]
Abstract
Breast cancer (BC) is one of the most common female malignant tumors. BC treatment depends on the use of chemotherapeutic drugs, causing various adverse effects. Increasing evidence has shown that natural polysaccharides (NPs) are potential adjuvants or substitutes for anti-BC drugs. However, the information regarding anti-BC NPs remains scattered. Thus, the recent progress in the structure, bioactivity, mechanism and application of anti-BC NPs is comprehensively summarized in this review. Moreover, the structure-activity relationship is discussed. Additionally, the prospects for future work are proposed. Recent studies have shown that anti-BC NPs have diverse structural features, which are affected by the extraction and purification methods. NPs show anti-BC activities in cell and animal experiments as well as in clinical researches, and enhance anti-BC effects of chemotherapeutic drugs in cell and animal experiments. The anti-BC mechanisms of NPs include anti-proliferation, inducing apoptosis, anti-metastasis and anti-invasion, immunoenhancement, gut microbiota regulation and others. The anti-BC activities of NPs are influenced by molecular weight, monosaccharide composition, functional groups, glycosidic bond types, backbone and side chains. NPs-based nanoparticles, nanocarriers, drug delivery systems, nanocomposites and other materials can also be used in anti-BC. This review provides theoretical bases for future research and functional application of NPs in anti-BC.
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Affiliation(s)
- Xiao-Yin Wang
- School of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, China; Key Laboratory of Development and Utilization of Gannan Characteristic Food Function Component of Ganzhou, Gannan Medical University, Ganzhou, China.
| | - Ao-Qiu Chen
- School of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, China.
| | - Jing Huang
- School of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, China.
| | - Jiang-Hong Luo
- School of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, China; Key Laboratory of Development and Utilization of Gannan Characteristic Food Function Component of Ganzhou, Gannan Medical University, Ganzhou, China.
| | - Qi Zou
- School of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, China; Key Laboratory of Development and Utilization of Gannan Characteristic Food Function Component of Ganzhou, Gannan Medical University, Ganzhou, China.
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Liu X, Yang F, Ren P, Lv W, Chen B, Niu B, Ren Y, Wang L, Sun M, Zuo Z, Li J, Geng A. Study on the mechanism of macrophages activated by phosphoesterified rehmanniae polysaccharide on human gastric cancer cells. Int J Biol Macromol 2024; 277:133952. [PMID: 39029829 DOI: 10.1016/j.ijbiomac.2024.133952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 07/14/2024] [Accepted: 07/16/2024] [Indexed: 07/21/2024]
Abstract
Gastric cancer(GC)is one of the most common gastrointestinal malignant tumors in the world, requiring the development of novel therapeutic agents with reduced toxicity. Rehmannia polysaccharide (RPS) possesses immunomodulatory and anti-tumor properties, yet its efficacy is suboptimal. To enhance its biological activity, we subjected RPS to molecular modifications, resulting in phosphorylated Rehmannia polysaccharides (P-RPS). Using the mixed phosphate method, we synthesized P-RPS and optimized the synthesis conditions through a combination of single-factor and response surface methodologies. In vitro studies on P-RPS's anti-tumor activity showed no direct influence on the viability of GC cells. However, P-RPS induced the transformation of PMA-activated THP-1 cells into the M1 phenotype. We collected conditioned medium (CM) of THP-1 cells to stimulate gastric cancer cells and CM-P-RPS significantly promoted apoptosis of gastric cancer cells and inhibited cell proliferation, and reduced cell migration. Mechanistically, CM-P-RPS inhibits the Wnt/β-catenin signaling pathway through LGR6, leading to the suppression of tumor growth. Furthermore, P-RPS demonstrated a significant inhibitory effect on tumor growth in vivo, suggesting its potential as a promising therapeutic agent for GC treatment.
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Affiliation(s)
- Xianglong Liu
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xian 712046, China
| | - Feng Yang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xian 712046, China
| | - Pengyu Ren
- Institute of Medical Research, Northwestern Polytechnical University, Xian 710072, China; Sanhang Institute for Brain Science and Technology, Northwestern Polytechnical University, Xian 710072, China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen 518057, China
| | - Wenbo Lv
- Institute of Medical Research, Northwestern Polytechnical University, Xian 710072, China; Sanhang Institute for Brain Science and Technology, Northwestern Polytechnical University, Xian 710072, China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen 518057, China
| | - Bodong Chen
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xian 712046, China
| | - Ben Niu
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xian 712046, China
| | - Yongyong Ren
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xian 712046, China
| | - Lu Wang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xian 712046, China
| | - Meng Sun
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xian 712046, China
| | - Zhenyu Zuo
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xian 712046, China
| | - Jin Li
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xian 712046, China.
| | - Anqi Geng
- Institute of Medical Research, Northwestern Polytechnical University, Xian 710072, China; Sanhang Institute for Brain Science and Technology, Northwestern Polytechnical University, Xian 710072, China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen 518057, China.
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Lu M, Guo XW, Zhang FF, Wu DH, Xie D, Luo FQ. Dexmedetomidine ameliorates diabetic intestinal injury by promoting the polarization of M2 macrophages through the MMP23B pathway. World J Diabetes 2024; 15:1962-1978. [PMID: 39280187 PMCID: PMC11372634 DOI: 10.4239/wjd.v15.i9.1962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 07/17/2024] [Accepted: 08/12/2024] [Indexed: 08/27/2024] Open
Abstract
BACKGROUND Diabetes is often associated with gastrointestinal dysfunctions, which can lead to hypoglycemia. Dexmedetomidine (DEX) is a commonly used sedative in perioperative diabetic patients and may affect gastrointestinal function. AIM To investigate whether sedative doses of DEX alleviate diabetes-caused intestinal dysfunction. METHODS Sedation/anesthesia scores and vital signs of streptozotocin (STZ)-induced diabetic mice under DEX sedation were observed. Diabetic mice were divided into saline and DEX groups. After injecting sedatives intraperitoneally, tight junctions (TJs) and apoptotic levels were evaluated 24 hours later to assess the intestinal barrier function. The role of DEX was validated using Villin-MMP23B flox/flox mice with intestinal epithelial deletion. In vitro, high glucose and hyperosmolarity were used to culture Caco-2 monolayer cells with STZ inter-vention. Immunofluorescence techniques were used to monitor the barrier and mitochondrial functions. RESULTS MMP23B protein levels in the intestinal tissue of STZ-induced diabetic mice were significantly higher than those in the intestinal tissue of control mice, with the DEX group displaying decreased MMP23B levels. Diabetes-mediated TJ dis-ruption, increased intestinal mucosal permeability, and systemic inflammation in wild-type mice might be reversed by DEX. In Caco-2 cells, MMP23B was associated with increased reactive oxygen species accumulation, mitochondrial membrane potential depolarization, and TJ disruption. CONCLUSION DEX reduces MMP23B, which may potentially contribute to STZ-induced intestinal barrier dysfunction, affecting TJ modification through mitochondrial dysfunction.
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Affiliation(s)
- Man Lu
- Department of Anesthesiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou 310006, Zhejiang Province, China
| | - Xiao-Wen Guo
- Department of Anesthesiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou 310006, Zhejiang Province, China
| | - Fang-Fang Zhang
- Department of Anesthesiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou 310006, Zhejiang Province, China
| | - Dan-Hong Wu
- Department of Anesthesiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou 310006, Zhejiang Province, China
| | - Di Xie
- Department of Emergency, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Feng-Qin Luo
- Department of Anesthesiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou 310006, Zhejiang Province, China
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Varady SR, Greiner D, Roh-Johnson M. Macrophage subtypes inhibit breast cancer proliferation in culture. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.06.01.596963. [PMID: 38853881 PMCID: PMC11160732 DOI: 10.1101/2024.06.01.596963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2024]
Abstract
Macrophages are a highly plastic cell type that adopt distinct subtypes and functional states depending on environmental cues. These functional states can vary wildly, with distinct macrophages capable of displaying opposing functions. We sought to understand how macrophage subtypes that exist on two ends of a spectrum influence the function of other cells. We used a co-culture system with primary human macrophages to probe the effects of macrophage subtypes on breast cancer cell proliferation. Our studies revealed a surprising phenotype in which both macrophage subtypes inhibited cancer cell proliferation compared to cancer cells alone. Of particular interest, using two different proliferation assays with two different breast cancer cell lines, we showed that differentiating macrophages into a "pro-tumor" subtype inhibited breast cancer cell proliferation. These findings are inconsistent with the prevailing interpretation that "pro-tumor" macrophages promote cancer cell proliferation and suggest a re-evaluation of how these interpretations are made.
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Affiliation(s)
- Sophia R.S. Varady
- Department of Biochemistry, University of Utah School of Medicine; Salt Lake City, UT, 84112, USA
| | - Daniel Greiner
- Department of Biochemistry, University of Utah School of Medicine; Salt Lake City, UT, 84112, USA
| | - Minna Roh-Johnson
- Department of Biochemistry, University of Utah School of Medicine; Salt Lake City, UT, 84112, USA
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Thipe VC, Jatar A, Raphael Karikachery A, Katti KK, Katti KV. Green Nanotechnology of Yucca filamentosa- Phytochemicals-Functionalized Gold Nanoparticles-Antitumor Efficacy Against Prostate and Breast Cancers. Nanotechnol Sci Appl 2023; 16:19-40. [PMID: 38106675 PMCID: PMC10723618 DOI: 10.2147/nsa.s437812] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 11/29/2023] [Indexed: 12/19/2023] Open
Abstract
Purpose We report an innovative green nanotechnology utilizing an electron-rich cocktail of phytochemicals from Yucca filamentosa L. to synthesize biocompatible gold nanoparticles without the use of any external chemical reducing agents and evaluate their anti-cancer activity. Methods Yucca filamentosa L. extract, containing a cocktail of phytochemicals, was prepared, and used to transform gold salt into Y. filamentosa phytochemicals encapsulated gold nanoparticles (YF-AuNPs). Additionally, gum arabic stabilized YF-AuNPs (GAYF-AuNPs) were also prepared to enhance the in vitro/in vivo stability. Anticancer activity was evaluated against prostate (PC-3) and breast (MDAMB-231) cancer cell lines. Targeting abilities of gold nanoparticles were tested using pro-tumor macrophage cell lines. Results Comprehensive characterization of new nanomedicine agents YF-AuNPs and GAYF-AuNPs revealed spherical, and monodisperse AuNPs with moderate zeta potentials (-19 and -20 mV, respectively), indicating in vitro/in vivo stability. The core size of YF-AuNPs (14 ± 5 nm) and GAYF-AuNPs (10 ± 5 nm) is suitable for optimal penetration into tumor cells through both enhanced permeability and retention (EPR) effect as well as through the receptor mediated endocytosis. Notably, YF-AuNPs exhibited potent anticancer activity against prostate (PC-3) and breast tumors (MDAMB-231) by inducing early and late apoptotic stages. Moreover, YF-AuNPs resulted in elevated levels of anti-tumor cytokines (TNF-α and IL-12) and reduced levels of pro-tumor cytokines (IL-6 and IL-10), provide compelling evidence on the immunomodulatory property of YF-AuNPs. Conclusion Overall, these Y. filamentosa phytochemicals functionalized nano-Ayurvedic medicine agents demonstrated selective toxicity to cancer cells while sparing normal cells. Most notably, to our knowledge, this is the first study that shows YF-AuNP's targeting efficacy toward pro-tumor macrophage cell lines, suggesting an immunomodulatory pathway for cancer treatment. This work introduces a novel avenue for herbal and nano-Ayurvedic approaches to human cancer treatment, mediated through selective efficacy and immunomodulatory potential.
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Affiliation(s)
- Velaphi C Thipe
- Institute of Green Nanotechnology, University of Missouri, Columbia, MO, 65212, USA
- Department of Radiology, University of Missouri, Columbia, MO, 65212, USA
| | - Ananya Jatar
- Institute of Green Nanotechnology, University of Missouri, Columbia, MO, 65212, USA
| | - Alice Raphael Karikachery
- Institute of Green Nanotechnology, University of Missouri, Columbia, MO, 65212, USA
- Department of Radiology, University of Missouri, Columbia, MO, 65212, USA
| | - Kavita K Katti
- Institute of Green Nanotechnology, University of Missouri, Columbia, MO, 65212, USA
- Department of Radiology, University of Missouri, Columbia, MO, 65212, USA
| | - Kattesh V Katti
- Institute of Green Nanotechnology, University of Missouri, Columbia, MO, 65212, USA
- Department of Radiology, University of Missouri, Columbia, MO, 65212, USA
- Department of Physics, University of Missouri, Columbia, MO, 65211, USA
- Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, 65212, USA
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Shettigar A, Salunke R, Modi D, Mukherjee N. Targeting molecular cross-talk between tumor cells and tumor associated macrophage as therapeutic strategy in triple negative breast cancer. Int Immunopharmacol 2023; 119:110250. [PMID: 37163922 DOI: 10.1016/j.intimp.2023.110250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 04/16/2023] [Accepted: 04/25/2023] [Indexed: 05/12/2023]
Abstract
Triple-negative Breast cancer (TNBC) is a subtype of breast cancer (BC) that lacks expression for ER/PR/Her2 receptors and is associated with aggressive disease pathogenesis and the worst prognosis among other subtypes of BC. Accumulating evidence-based studies indicate the high immunogenic ability of TNBC tumors and the applicability of immunotherapeutic strategies to overcome therapy resistance and tumor recurrence in TNBC patients. However, not all TNBC patients respond equally well to current immunotherapies that mainly target the adaptive immune system for tumor rejection. Recent studies are contemplating the efficacy of tumor-associated macrophage (TAM) targeted therapies since these subpopulations of cells comprise one of the major components of tumor-infiltrating immune cells (TIIs) in the TNBC tumor microenvironment (TME) and play an essential role in priming the adaptive immune response mediators towards both antitumorigenic and pro-tumorigenic response facilitated by intercellular cross-talk between tumor cells and TAM populations present within TNBC-TME. The present review discusses these molecular mechanisms and their consequence on the progression of TNBC tumors. Also, the therapeutic strategies targeting candidate genes/pathways involved in molecular cross-talk between TAM-TNBC cells and their impact on the development and progression of TNBC tumors are also discussed.
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Affiliation(s)
- Anusha Shettigar
- Department of Molecular and Cellular Biology, National Institute for Research in Reproductive and Child Health, Mumbai, India
| | - Rushigandha Salunke
- Department of Molecular and Cellular Biology, National Institute for Research in Reproductive and Child Health, Mumbai, India
| | - Deepak Modi
- Department of Molecular and Cellular Biology, National Institute for Research in Reproductive and Child Health, Mumbai, India
| | - Nupur Mukherjee
- Department of Molecular and Cellular Biology, National Institute for Research in Reproductive and Child Health, Mumbai, India.
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Jędrzejewski T, Pawlikowska M, Sobocińska J, Wrotek S. COVID-19 and Cancer Diseases-The Potential of Coriolus versicolor Mushroom to Combat Global Health Challenges. Int J Mol Sci 2023; 24:ijms24054864. [PMID: 36902290 PMCID: PMC10003402 DOI: 10.3390/ijms24054864] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 02/09/2023] [Accepted: 02/28/2023] [Indexed: 03/06/2023] Open
Abstract
Coriolus versicolor (CV) is a common species from the Polyporaceae family that has been used in traditional Chinese herbal medicine for over 2000 years. Among well-described and most active compounds identified in CV are polysaccharopeptides, such as polysaccharide peptide (PSP) and Polysaccharide-K (PSK, krestin), which, in some countries, are already used as an adjuvant agent in cancer therapy. In this paper, research advances in the field of anti-cancer and anti-viral action of CV are analyzed. The results of data obtained in in vitro and in vivo studies using animal models as well as in clinical research trials have been discussed. The present update provides a brief overview regarding the immunomodulatory effects of CV. A particular focus has been given to the mechanisms of direct effects of CV on cancer cells and angiogenesis. A potential use of CV compounds in anti-viral treatment, including therapy against COVID-19 disease, has also been analyzed based on the most recent literature. Additionally, the significance of fever in viral infection and cancer has been debated, providing evidence that CV affects this phenomenon.
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Lowenthal R, Taylor M, Gidden JA, Heflin B, Lay JO, Avaritt N, Tackett AJ, Urbaniak A. The mycelium of the Trametes versicolor synn. Coriolus versicolor (Turkey tail mushroom) exhibit anti-melanoma activity in vitro. Biomed Pharmacother 2023; 161:114424. [PMID: 36827712 PMCID: PMC10147383 DOI: 10.1016/j.biopha.2023.114424] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 02/16/2023] [Accepted: 02/17/2023] [Indexed: 02/24/2023] Open
Abstract
Melanoma is one of the most aggressive forms of skin cancer and is characterized by high metastatic potential. Despite improvements in early diagnosis and treatment, the mortality rate among metastatic melanoma patients continues to represent a significant clinical challenge. Therefore, it is imperative that we search for new forms of treatment. Trametes versicolor is a mushroom commonly used in Chinese traditional medicine due to its numerous beneficial properties. In the present work, we demonstrate T. versicolor fruiting body and mycelium ethanol extracts exhibit potent cytotoxic activity towards A375 (IC50 = 663.3 and 114.5 µg/mL respectively) and SK-MEL-5 (IC50 = 358.4 and 88.6 µg/mL respectively) human melanoma cell lines. Further studies revealed that T. versicolor mycelium extract induced apoptotic cell death and poly (ADP-ribose) polymerase cleavage, upregulated the expression of autophagy-associated marker LC3-II, increased the presentation of major histocompatibility complex II and expression of programmed death-ligand receptor, and inhibited cell migration in SK-MEL-5 cells. Therefore, our present findings highlight the therapeutic potential of T. versicolor mycelium extract for the treatment of melanoma and merit further study.
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Affiliation(s)
- Rocky Lowenthal
- Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States
| | - Megan Taylor
- Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States
| | - Jennifer A Gidden
- Arkansas Statewide MS Facility, University of Arkansas, Fayetteville 72701, AR, United States
| | - Billie Heflin
- Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States
| | - Jackson O Lay
- Arkansas Statewide MS Facility, University of Arkansas, Fayetteville 72701, AR, United States; Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville 72701, AR, United States
| | - Nathan Avaritt
- Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States
| | - Alan J Tackett
- Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
| | - Alicja Urbaniak
- Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
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Jędrzejewski T, Sobocińska J, Pawlikowska M, Dzialuk A, Wrotek S. Dual Effect of the Extract from the Fungus Coriolus versicolor on Lipopolysaccharide-Induced Cytokine Production in RAW 264.7 Macrophages Depending on the Lipopolysaccharide Concentration. J Inflamm Res 2022; 15:3599-3611. [PMID: 35757459 PMCID: PMC9231549 DOI: 10.2147/jir.s364945] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 05/26/2022] [Indexed: 12/13/2022] Open
Abstract
Purpose Extract from the fungus Coriolus versicolor (CV) is classified as an immunological response modifier. Previously, we have shown that this extract induces interleukin 6 (IL-6)-related extension of lipopolysaccharide (LPS)-induced fever. This study investigated the effect of CV extract on the production of pro-inflammatory cytokines and the expression of components of signal transduction pathways leading to the secretion of cytokines from RAW 264.7 macrophages stimulated with different doses of LPS. Methods RAW 264.7 cells were stimulated with CV extract alone or co-treated with CV extract and LPS. The level of IL-6 and tumour necrosis factor α (TNF-α) in the culture media was measured using ELISA. Protein expression of Toll-like receptor (TLR) 4, phosphorylated IκB (p-IκB), CD14 glycoprotein and phospho-phosphatidylinositol 3-kinase (p-PI3K) was evaluated using Western blot. The effects of TLR4, nuclear factor κB (NF-κB) and p-PI3K on cytokine secretion were estimated using inhibitors: TAK-242, JSH-23 and LY294002. Results CV extract itself stimulates the secretion of IL-6 and TNF-α and increases the expression of TLR4, p-IκB and p-PI3K. The presence of CV extract during the treatment of cells with lower concentrations of LPS (10 and 100 ng/mL) increases the cytokine production. Co-stimulation of cells with CV extract and LPS at a higher dose (500 ng/mL) decreases the secretion of cytokines. This effect is related to the changes in the expression of TLR4, CD14 glycoprotein, p-IκB and p-PI3K. Conclusion This is the first report showing that the CV extract-induced production of cytokines is mediated by the PI3K signalling pathway. This extract acts antagonistically or additively with LPS on the production of IL-6 and TNF-α, depending on the LPS concentration. Our results are helpful for illustrating the mechanisms for the immunostimulatory effect of CV extract in inflammatory processes.
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Affiliation(s)
- Tomasz Jędrzejewski
- Department of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Torun, 87-100, Poland
| | - Justyna Sobocińska
- Department of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Torun, 87-100, Poland
| | - Małgorzata Pawlikowska
- Department of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Torun, 87-100, Poland
| | - Artur Dzialuk
- Department of Genetics, Faculty of Biological Sciences, Kazimierz Wielki University, Bydgoszcz, 85-090, Poland
| | - Sylwia Wrotek
- Department of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Torun, 87-100, Poland
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Xu J, Shen R, Jiao Z, Chen W, Peng D, Wang L, Yu N, Peng C, Cai B, Song H, Chen F, Liu B. Current Advancements in Antitumor Properties and Mechanisms of Medicinal Components in Edible Mushrooms. Nutrients 2022; 14:nu14132622. [PMID: 35807802 PMCID: PMC9268676 DOI: 10.3390/nu14132622] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 06/19/2022] [Accepted: 06/22/2022] [Indexed: 02/01/2023] Open
Abstract
Edible and medicinal fungi, a group of eukaryotic organisms with numerous varieties, including Coriolus versicolor, Ganoderma lucidum, Cordyceps sinensis, Pleurotus ostreatus, and Grifola frondosa, have been demonstrated to possess a board range of pharmaceutical properties, including anti-virus, anti-inflammation, and neuroprotection. Moreover, edible and medicinal fungi have been traditionally consumed as food to provide multiple nutrients and as drugs owing to having the activities of invigorating blood circulation, reinforcing the healthy qi, clearing away heat, and eliminating stasis for thousands of years in China. Malignant tumors, well-known as the second leading cause of death globally, accounted for nearly 10 million deaths in 2020. Thus, in-depth exploration of strategies to prevent and treat cancer is extremely urgent. A variety of studies have reported that the main bioactive components of edible and medicinal fungi, mainly polysaccharides and triterpenoids, exhibit diverse anticancer activities via multiple mechanisms, including inhibition of cell proliferation and metastasis, induction of apoptosis and autophagy, reversing multidrug resistance, and regulation of immune responses, thus suggesting their substantial potential in the prevention and treatment of cancer. Our review summarizes the research progress on the anticancer properties of edible and medicinal fungi and the underlying molecular mechanism, which may offer a better understanding of this field. Additionally, few studies have reported the safety and efficacy of extracts from edible and medicinal fungi, which may limit their clinical application. In summary, there is a need to continue to explore the use of those extracts and to further validate their safety and efficacy.
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Affiliation(s)
- Jing Xu
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; (J.X.); (R.S.); (Z.J.); (B.C.)
| | - Rui Shen
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; (J.X.); (R.S.); (Z.J.); (B.C.)
| | - Zhuoya Jiao
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; (J.X.); (R.S.); (Z.J.); (B.C.)
| | - Weidong Chen
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; (W.C.); (D.P.); (L.W.); (N.Y.); (C.P.)
| | - Daiyin Peng
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; (W.C.); (D.P.); (L.W.); (N.Y.); (C.P.)
| | - Lei Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; (W.C.); (D.P.); (L.W.); (N.Y.); (C.P.)
| | - Nianjun Yu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; (W.C.); (D.P.); (L.W.); (N.Y.); (C.P.)
| | - Can Peng
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; (W.C.); (D.P.); (L.W.); (N.Y.); (C.P.)
| | - Biao Cai
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; (J.X.); (R.S.); (Z.J.); (B.C.)
| | - Hang Song
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; (J.X.); (R.S.); (Z.J.); (B.C.)
- Correspondence: (B.L.); (H.S.); (F.C.)
| | - Fengyuan Chen
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; (J.X.); (R.S.); (Z.J.); (B.C.)
- Correspondence: (B.L.); (H.S.); (F.C.)
| | - Bin Liu
- Cancer Research Center, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China
- Correspondence: (B.L.); (H.S.); (F.C.)
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Pawlikowska M, Jędrzejewski T, Slominski AT, Brożyna AA, Wrotek S. Pigmentation Levels Affect Melanoma Responses to Coriolus versicolor Extract and Play a Crucial Role in Melanoma-Mononuclear Cell Crosstalk. Int J Mol Sci 2021; 22:ijms22115735. [PMID: 34072104 PMCID: PMC8198516 DOI: 10.3390/ijms22115735] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 05/20/2021] [Accepted: 05/25/2021] [Indexed: 02/07/2023] Open
Abstract
Melanoma, the malignancy originating from pigment-producing melanocytes, is the most aggressive form of skin cancer and has a poor prognosis once the disease starts to metastasize. The process of melanin synthesis generates an immunosuppressive and mutagenic environment, and can increase melanoma cell resistance to different treatment modalities, including chemo-, radio- or photodynamic therapy. Recently, we have shown that the presence of melanin pigment inhibits the melanoma cell response to bioactive components of Coriolus versicolor (CV) Chinese fungus. Herein, using the same human melanoma cell line in which the level of pigmentation can be controlled by the L-tyrosine concentration in culture medium, we tested the effect of suppression of melanogenesis on the melanoma cell response to CV extract and investigated the cell death pathway induced by fungus extract in sensitized melanoma cells. Our data showed that susceptibility to CV-induced melanoma cell death is significantly increased after cell depigmentation. To the best of our knowledge, we are the first to demonstrate that CV extract can induce RIPK1/RIPK3/MLKL-mediated necroptosis in depigmented melanoma cells. Moreover, using the co-culture system, we showed that inhibition of the tyrosinase activity in melanoma cells modulates cytokine expression in co-cultured mononuclear cells, indicating that depigmentation of melanoma cells may activate immune cells and thereby influence a host anticancer response.
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Affiliation(s)
- Małgorzata Pawlikowska
- Department of Immunology, Faculty of Biology and Veterinary Sciences, Nicolaus Copernicus University, 87-100 Toruń, Poland; (T.J.); (S.W.)
- Correspondence: ; Tel.: +48-(56)-611-25-15
| | - Tomasz Jędrzejewski
- Department of Immunology, Faculty of Biology and Veterinary Sciences, Nicolaus Copernicus University, 87-100 Toruń, Poland; (T.J.); (S.W.)
| | - Andrzej T. Slominski
- Department of Dermatology, Comprehensive Cancer Center, Cancer Chemoprevention Program, University of Alabama at Birmingham, Birmingham, AL 35294, USA;
- Laboratory Service of the VA Medical Center, Birmingham, AL 35294, USA
| | - Anna A. Brożyna
- Department of Human Biology, Faculty of Biology and Veterinary Sciences, Nicolaus Copernicus University, 87-100 Toruń, Poland;
| | - Sylwia Wrotek
- Department of Immunology, Faculty of Biology and Veterinary Sciences, Nicolaus Copernicus University, 87-100 Toruń, Poland; (T.J.); (S.W.)
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Extract from the Coriolus versicolor Fungus as an Anti-Inflammatory Agent with Cytotoxic Properties against Endothelial Cells and Breast Cancer Cells. Int J Mol Sci 2020; 21:ijms21239063. [PMID: 33260615 PMCID: PMC7731170 DOI: 10.3390/ijms21239063] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 11/24/2020] [Accepted: 11/27/2020] [Indexed: 12/13/2022] Open
Abstract
Chronic inflammation is a well-recognised tumour-enabling component, which includes bioactive molecules from cells infiltrating the tumour microenvironment and increases the risk of cancer progression. Since long-term use of the currently available anti-inflammatory drugs used in cancer therapy causes numerous side effects, the aim of this study was to investigate the effect of an extract isolated from the Coriolus versicolor fungus (CV extract) on HUVEC endothelial cells and MCF-7 breast cancer cells in a pro-inflammatory microenvironment mimicked by lipopolysaccharide (LPS). The cells were simultaneously stimulated with the LPS and CV extract. After co-treatment, the cell viability, generation of reactive oxygen species (ROS), wound-healing assay, production of the pro-inflammatory and pro-angiogenic factors (interleukin (IL) 6, IL-8, and metalloproteinase (MMP) 9)), as well as expression of Toll-like receptor (TLR) 4 and phosphorylated IκB (p-IκB) were evaluated. The results showed that the CV extract inhibited IL-6, IL-8, and MMP-9 production by the LPS-stimulated cells. This effect was accompanied by a decrease in TLR4 and p-IκB expression. The CV extract also had anti-migratory properties and induced a cytotoxic effect on the cells that was enhanced in the presence of LPS. The observed cytotoxicity was associated with an increase in ROS generation. We conclude that the CV extract possesses cytotoxic activity against cancer cells and endothelial cells and has the ability to inhibit the expression of the pro-tumorigenic factors associated with inflammation.
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