title: Genistein regulates tumor microenvironment and exhibits anticancer effect in dimethyl hydrazine-induced experimental colon carcinogenesis.
abstract: Colon cancer is one of the leading causes of cancer mortality, worldwide. Cancer stem cells are attractive targets for therapeutic interventions since their abnormal growth may trigger tumor initiation, progression, and recurrence. Colon cancer in rats were induced with 1, 2-dimethyl hydrazine (DMH) and treated with genistein, an isoflavone rich in the soy food products, which also possesses various biological activities. Genistein treatment regulates enzymatic and non-enzymatic anti-oxidants in the DMH-induced colonic tissue microenvironment. Alcian blue staining in colonic tissue reveals that mucin secretion was found to be depleted in DMH-induced group of animals. The alterations were normalized in the genistein-treated groups. Also, the mast cell population and collagen deposition were reduced as compared to induced group. Genistein treatment reduces the prognostic marker Argyrophilic nuclear organizer region (AgNOR) and proliferating cell nucleolar antigen (PCNA) in DMH-induced group of rats. DMH administration induces oxidative stress, whereas genistein activates nuclear factor-erythroid 2 related factor 2 (Nrf-2) and its downstream target hemoxygenase-1 (HO-1). Colonic stem cell marker protein CD133, CD44, and β-catenin expressions were found to be increased in DMH-induced group of animals as compared to control group of rats. Genistein treatment suppressed the expression of these stem cell markers suggesting rapid dysfunctional activation and proliferation of colonic stem cell-induced by DMH. The results of this study indicate that genistein administration in rats restored the colonic niche that was damaged by DMH and inhibits colon cancer progression. © 2016 BioFactors, 42(6):623-637, 2016.
authors.affiliation: Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600 025, India.
authors.forename: Vasudevan
authors.initials: V
authors.lastname: Sekar
authors.affiliation: Biological sciences, Biochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai, 600 020, India.
authors.forename: Suresh Kumar
authors.initials: SK
authors.lastname: Anandasadagopan
authors.affiliation: Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600 025, India.|Centre for Stem Cell Research in the Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600 025, India.
authors.forename: Sudhandiran
authors.initials: S
authors.lastname: Ganapasam
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D058739:Aberrant Crypt Foci / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D063646:Carcinogenesis / Q000187:drug effects / Q000473:pathology; D049109:Cell Proliferation; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004127:Dimethylhydrazines; D004354:Drug Screening Assays, Antitumor; D024022:Fibrillar Collagens / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism; D008297:Male; D009077:Mucins / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017208:Rats, Wistar; D059016:Tumor Microenvironment / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D000970:Antineoplastic Agents; D000975:Antioxidants; C495268:Ctnnb1 protein, rat; D004127:Dimethylhydrazines; D024022:Fibrillar Collagens; D018960:Hyaluronan Receptors; D009077:Mucins; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D018809:Proliferating Cell Nuclear Antigen; D051176:beta Catenin; D019833:Genistein; D051547:Heme Oxygenase-1
keywords: Nrf-2; colon cancer; dimethylhydrazine; genistein; microenvironment