Modulating effect of Withania somnifera on TCA cycle enzymes and electron transport chain in azoxymethane-induced colon cancer in mice

• Published in: Immunopharmacology and immunotoxicology 2010-09, Vol.32 (3), p.523-527
• Main Authors: Muralikrishnan, Govidan, Amanullah, Safiullah, Basha, Mohamed I., Dinda, Amit K., Shakeel, Faiyaz
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents, Phytogenic - therapeutic use; Azoxymethane; Azoxymethane - toxicity; Citric Acid Cycle - drug effects; colon cancer; Colonic Neoplasms - chemically induced; Colonic Neoplasms - drug therapy; Colonic Neoplasms - enzymology; Electron Transport - drug effects; electron transport chain complexes; Male; Mice; Mice, Inbred Strains; Plant Extracts - therapeutic use; TCA cycle enzymes; Withania; withania somnifera
• ISSN: 0892-3973; 1532-2513
• DOI: 10.3109/08923970903581540

The aim of the present investigation was to evaluate the efficacy of Withania somnifera on tricarboxylic acid (TCA) cycle enzymes and electron transport chain in azoxymethane-induced experimental colon cancer in mice. Azoxymethane at the dose of 15 mg/kg body weight was induced intraperitoneally once in a week for 28 days. The progression in colon tumor development was correlated with the appearance of the histological biomarker and aberrant crypt foci (ACF). Azoxymethane-induced colon cancer animals were treated with 400 mg/kg body weight of W. somnifera once in a week orally for 28 days. After the experimental period, the animals were killed and analyzed for TCA cycle key enzymes, such as isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and α-keto glutarate dehydrogenase (α-KGDH). The modulating effect of W. somnifera on TCA cycle key enzymes and electron transport chain complexes were investigated against colon cancer induced by azoxymethane in Swiss albino mice. Decreased activities of TCA cycle key enzymes such as ICDH, SDH, MDH, and α-KGDH in colon cancer bearing animals were observed. W. somnifera administration normalized these enzyme levels in azoxymethane-induced experimental mice. These results suggested that W. somnifera is the promising chemotherapeutic agent for the treatment of colon cancer.