title: Antiproliferative and apoptotic-inducing potential of ellagic acid against 1,2-dimethyl hydrazine-induced colon tumorigenesis in Wistar rats.
abstract: Colon cancer remains one of the major worldwide causes of cancer-related morbidity and mortality in Western countries and is increasingly common in Asia. Ellagic acid (EA), a major component of polyphenol possesses attractive remedial features. The aim of this study is to divulge the potential effect of EA during 1,2-dimethyl hydrazine (DMH)-induced colon cancer in male Wistar albino rats. The rats were segregated into four groups: group I, control rats; group II, rats received EA (60 mg/kg b.wt./day, orally); rats in group III, induced with DMH (20 mg/kg b.wt.) subcutaneously for 15 weeks; DMH-induced group IV rats were initiated with EA treatment. Colon of the rats treated with DMH exhibited higher glycoconjugates and proliferation index such as elevated expressions of argyrophilic nucleolar organizing regions (AgNORs), proliferating cell nuclear antigen (PCNA), cyclin D1, matrix metalloproteins (MMP-2 and -9), and mast cells. DMH induction also increased phase I-metabolizing enzymes with simultaneous decrease in the phase II detoxifying enzymes. In contrast, dietary administration of EA significantly (p < 0.05) down regulated the proliferation index and restored back the levels of biotransformation enzymes. The carcinogenic insult also altered the expression of pro-apoptotic protein p53, whereas dietary EA administration significantly (p < 0.01) up regulates p53 expression to further induce apoptotic pathway. Ultrastructural changes in colon were also in accord with the above aberrations. Overall findings suggested that the suppression of colon cancer by EA in vivo involves inhibition of cell proliferation, activation of apoptosis, and efficient detoxification.
authors.affiliation: Department of Biochemistry, Cell Biology Unit, University of Madras, Maraimalai Campus, Guindy, Chennai, 600025, Tamil Nadu, India.
authors.forename: Syed
authors.initials: S
authors.lastname: Umesalma
authors.forename: Ponnuraj
authors.initials: P
authors.lastname: Nagendraprabhu
authors.forename: Ganapasam
authors.initials: G
authors.lastname: Sudhandiran
mesh_terms: D019813:1,2-Dimethylhydrazine; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D019938:Cyclin D1 / Q000096:biosynthesis; D004610:Ellagic Acid / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D004610:Ellagic Acid; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D019813:1,2-Dimethylhydrazine