Abstract LB-270: Screening of novel phytochemical/s that can protect breast epithelial cells from PhIP induced cytotoxicity

Abstract

Abstract Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) is a known food carcinogen abundantly found in cooked meat. Several studies have shown that PhIP can induce tumors in breast, prostate and colon cells and rodent models. Metabolism of PhIP results in the formation of free radicals (ROS) and PhIP metabolites are known to produce DNA adduct and DNA strand breaks. The metabolism and mutational effects of PhIP are well defined. Phytochemicals are known to inhibit cytotoxic and genotoxic effects. Therefore, we hypothesized that the right combination of antioxidants and or phytochemical (naturally present in fruits, vegetables and spices) along with grilled meat should be capable of suppressing the PhIP induced cytotoxicity and development of breast cancer. Therefore, a model system using human breast epithelial cells (MCF 10A) was developed to mimic the cellular changes and test various antioxidants in presence or absence of PhIP. We have tested four vitamins (C, K3, D3, and E), Gingerol (6 and 10), N-acetyl cysteine, glutathione and curcumin at varying concentrations. The protective effect of these compounds was evaluated using cell viability assay, DCF assay to quantify ROS production, Comet assay to quantify the DNA damage and DNA adduct formation by immunofluorescence method. Results indicate that presence of these compounds improves cell viability as compared to PhIP treated group. However, curcumin showed significant differences and PhIP induced cell cytotoxicity was consistently reverted to normal in presence of Curcumin. Gene expression analysis using RT PCR technique indicates that curcumin interact via multi molecular targets. Hence, the present study suggests that Curcumin is a promising natural compound to regress the effect of PhIP induced cell cytotoxicity in breast cells. Citation Format: Ashok K. Jain. Screening of novel phytochemical/s that can protect breast epithelial cells from PhIP induced cytotoxicity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-270. doi:10.1158/1538-7445.AM2015-LB-270