P1.01-020 Chemopreventive Effect of Catechin Hydrates against Benzo(a)Pyrene Induced Lung Carcinogenesis in Mice: Plausible Role of ALDH1

Abstract

Lung cancer is a devastating disease with a poor prognosis. Chemoprevention has come out as a very promising protective strategy against cancer and numerous natural compounds in diet have shown their curative potential on lung cancer. Catechin is mainly found in green tea and possess anti-oxidative, anti-inflammatory and antiproliferative activity. The present study was designed to investigate the mechanism-based chemopreventive nature of catechin hydrate (CH) against B(a)P induced lung carcinogenesis in Swiss albino mice and possible role of aldehyde dehydrogenase 1 (ALDH1). B(a)P was administered orally (50 mg/kg body weight) twice a week for four successive weeks to induce lung cancer in mice. CH was supplemented to mice at doses of 20 and 40mg/kg b. wt. The body weight, lung weight, lactate dehydrogenase (LDH), lipid peroxidation (LPO), xanthine oxidase (XO), carcinoembryonic antigen (CEA), antioxidants armory activities (SOD, CAT, QR, GPx, GR, GST and GSH) were estimated. Further, histopathological analysis of lung tissue and Immunohistopathology analysis of ALDH1, VEGF, PCNA, NF-kB, COX-2, caspase-3 and Bcl-2 were also carried out. Administration of B(a)P resulted in increased XO, LPO, LDH, and CEA with subsequent decrease in activities of tissue anti-oxidant armory. It also resulted in up-regulation of VEGF, PCNA, NF-kB, COX-2, caspase-3 and down regulating Bcl-2. ALDH1 expression was also increased in B(a)P-induced lung cancer group. Pre-treatment with CH at a dose of 20 and 40 mg/kg b. wt. significantly decreased in XO, LDH, LPO, CEA and increased anti-oxidant armory. Moreover, assessment of protein expression revealed that CH pre-treatment effectively regulated hyperproliferation, inflammation and apoptosis in lung of mice. Immunohistochemical analysis also revealed that CH pre-treatment showed significantly reduced in ALDH1 expression. Further, the antiproliferative effect of CH was confirmed by histopathological analysis. Overall, Our findings suggest that catechin hydrate inhibits B(a)P-induced lung tumor formation by modulating hyperproliferation, inflammation, apoptosis and ALDH1 expression.