title: Chemopreventive effect of Amorphophallus campanulatus (Roxb.) blume tuber against aberrant crypt foci and cell proliferation in 1, 2-dimethylhydrazine induced colon carcinogenesis.
abstract: Colorectal cancer is one of the leading causes of cancer death, both in men and women. This study investigated the effects of Amorphophallus campanulatus tuber methanolic extract (ACME) on aberrant crypt foci (ACF) formation, colonic cell proliferation, lipid peroxidative damage and the antioxidant status in a long term preclinical model of 1, 2-dimethylhydrazine (DMH) induced colon carcinogenesis in rats. Male Wistar rats were divided into six groups, viz., group I rats served as controls; group II rats treated as drug controls receiving 250 mg/ kg body weight of ACME orally; group III rats received DMH (20 mg/kg body weight) subcutaneously once a week for the first 15 weeks; groups IV, V and VI rats received ACME along with DMH during the initiation, post- initiation stages and the entire period of the study, respectively. All the rats were sacrificed at the end of 30 weeks and the intestinal and colonic tissues from different groups were subjected to biochemical and histological studies. Administration of DMH resulted in significant (p ≤ 0.05) intestinal and colonic lipid peroxidation (MDA) and reduction of antioxidants such as catalase, glutathione peroxidase, glutathione reductase, glutathione-S- transferase and reduced glutathione. Whereas the supplementation of ACME significantly (p ≤ 0.05) improved the intestinal and colonic MDA and reduced glutathione levels and the activities of antioxidant enzymes in DMH intoxicated rats. ACME administration also significantly suppressed the formation and multiplicity of ACF. In addition, the DMH administered rats showed amplified expression of PCNA in the colon and decreased expression of this proliferative marker was clearly noted with initiation, post-initiation and entire period of ACME treatment regimens. These results indicate that ACME could exert a significant chemopreventive effect on colon carcinogenesis induced by DMH.
authors.affiliation: Biochemistry and Pharmacognosy Research Laboratory, School of Biosciences, Mahatma Gandhi University, Kerala, India E-mail : mslathasbs@yahoo.com.
authors.forename: Puthuparampil Nazarudeen
authors.initials: PN
authors.lastname: Ansil
authors.forename: Santhibhavan Prabhakaran
authors.initials: SP
authors.lastname: Prabha
authors.forename: Anand
authors.initials: A
authors.lastname: Nitha
authors.forename: Mukalel Sankunni
authors.initials: MS
authors.lastname: Latha
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D058739:Aberrant Crypt Foci / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D031056:Amorphophallus / Q000737:chemistry*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity; D002374:Catalase / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007124:Immunoenzyme Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002273:Carcinogens; D010936:Plant Extracts; D002374:Catalase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D019813:1,2-Dimethylhydrazine