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1.
ACS Pharmacol Transl Sci ; 7(3): 863-877, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38481680

ABSTRACT

Colon cancer is among the most lethal and prevalent malignant tumors in the world, and the lack of effective therapies highlights the need for novel therapeutic approaches. Schisandrin B (Sch B), a lignan extracted from the fruit ofSchisandra chinensis, has been reported for its anticancer properties. However, to date, no studies have been done to characterize the exact molecular mechanisms underlying the antitumorigenic effects of Sch B in colon cancer. This study aimed to explore the antitumorigenic effects of Sch B in colon cancer and to understand the underlying therapeutic mechanism. A comprehensive analysis of the molecular mechanism underlying the antitumorigenic effects of Sch B on human colon cancer cells was performed using a combination of Raman spectroscopy, RNA-seq, computational docking, and molecular biological experiments. The in vivo efficacy was evaluated by a mouse xenograft model. Sch B reduced cell proliferation and triggered apoptosis in human colon cancer cell lines. Raman spectroscopy, computational, RNA-seq, and molecular and cellular studies revealed that Sch B activated unfolded protein responses by interacting with CHOP and upregulating CHOP, which thereby induced apoptosis. CHOP knockdown alleviated the Sch B-induced reduction in cell viability and apoptosis. Sch B reduced colon tumor growth in vivo. Our findings demonstrated that Sch B induced apoptosis and inhibited cell proliferation and tumor growth in vitro and in vivo. These results provided an essential background for clinical trials examining the effects of Sch B in patients with colon cancer.

2.
Crit Rev Food Sci Nutr ; 62(24): 6549-6576, 2022.
Article in English | MEDLINE | ID: mdl-33819127

ABSTRACT

BACKGROUND: Endocrine-disrupting compounds (EDCs) are ubiquitous substances that are found in our everyday lives, including pesticides, plasticizers, pharmaceutical agents, personal care products, and also in food products and food packaging. Increasing epidemiological evidence suggest that EDCs may affect the development or progression of breast cancer and consequently lead to lifelong harmful health consequences, especially when exposure occurs during early life in humans. Yet so far no appraisal of the available evidence has been conducted on this topic. OBJECTIVE: To systematically review all the available epidemiological studies about the association of the levels of environmental exposures of EDCs with breast cancer risk. METHODS: The search was performed in accordance with the PRISMA guidelines. We retrieved articles from PubMed (MEDLINE) until 10 March 2021. The key words used in this research were: "Endocrine disruptor(s)" OR "Endocrine disrupting chemical(s)" OR any of the EDCs mentioned below AND "Breast cancer" to locate all relevant articles published. We included only cohort studies and case-control studies. All relevant articles were accessed in full text and were evaluated and summarized in tables. RESULTS: We identified 131 studies that met the search criteria and were included in this systematic review. EDCs reviewed herein included pesticides (e.g. p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodiphenyldichloroethylene (DDE), atrazine, 2,3,7,8-tetrachloridibenzo-p-dioxin (TCDD or dioxin)), synthetic chemicals (e.g. bisphenol A (BPA), phthalates, per- and polyfluoroalkyl substances (PFAS), parabens, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), contraceptive pills), phytoestrogens (e.g. genistein, resveratrol), and certain mycotoxins (e.g. zearalenone). Most studies assessed environmental EDCs exposure via biomarker measurements. CONCLUSION: We identified certain EDC exposures could potentially elevate the risk of breast cancer. As majority of EDCs are highly persistent in the environment and bio-accumulative, it is essential to assess the long-term impacts of EDC exposures, especially multi-generational and transgenerational. Also, since food is often a major route of exposure to EDCs, well-designed exposure assessments of potential EDCs in food and food packing are necessary and their potential link to breast cancer development need to be carefully evaluated for subsequent EDC policy making and regulations.


Subject(s)
Endocrine Disruptors , Environmental Pollutants , Neoplasms , Pesticides , Case-Control Studies , Endocrine Disruptors/toxicity , Environmental Exposure/adverse effects , Environmental Pollutants/toxicity , Epidemiologic Studies , Humans
3.
Crit Rev Food Sci Nutr ; 61(4): 690-711, 2021.
Article in English | MEDLINE | ID: mdl-32208932

ABSTRACT

Polyphenols are naturally occurring compounds in plants and they are the most abundant antioxidants in the human diet. Due to their considerable structural diversity, this largely influences their bioavailability. Since a large proportion of polyphenols remains unabsorbed along the gastrointestinal tract, they may accumulate in the large intestine, where most of them are extensively metabolized by the intestinal microbiota. The formation of bioactive polyphenol-derived metabolites may also benefit the health status of the subjects, although the mechanisms have not been delineated. This review aims to highlight the impact of polyphenols on gut health and the modes of action could be through modulation of intestinal barrier function, innate and adaptive immune response, signaling pathways, as well as the ability to modify gut microbiota composition. The review will conclude by presenting future perspective and challenges of polyphenols application in food products to be used for preventing or treating diseases.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Diet , Gastrointestinal Tract , Humans , Polyphenols/pharmacology
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