Abstract 1331: Green tea catechin suppression of carcinogenesis and cell proliferation induced by environmental carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene

Abstract

Abstract In this study we aim to identify the role of green tea catechins (GTCs) in early prevention of breast cell carcinogenesis induced chronically by environmental carcinogens. Most sporadic breast cancers are attributable to long-term exposure to environmental factors through a multi-year, multi-step, and multi-path disease process involving cumulative genetic and epigenetic alterations in progressive breast cell carcinogenesis. Epidemiologic and experimental studies have shown that GTCs may intervene with breast cancer development. However, the mechanisms for GTC prevention of cellular carcinogenesis induced by chronic exposure to environmental carcinogens remain to be elucidated. To study the activity of GTC components in suppression of cellular carcinogenesis, we used our cellular carcinogenesis model that mimics chronic breast cell carcinogenesis induced by cumulative exposures to low doses of the environmental carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P). We detected that the four major GTC components epicatechin (EC), epicatechin-3-gallate (ECG), epigallocatechin (EGC), and epigallocatechin-3-gallate (EGCG) at non-cytotoxic levels were able to suppress NNK- and B[a]P-induced cellular carcinogenesis, as measured by suppression of the acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, and increased cell mobility. We also detected that ECG was more effective than EC, EGC, and EGCG in suppression of cellular carcinogenesis. Investigating the mechanisms for GTCs in counteracting carcinogenic activity of NNK and B[a]P, we detected that all the catechins were able to suppress carcinogen-induced reactive oxygen species (ROS), resulting in suppressing ROS-induced ERK pathway activation, cell proliferation, DNA damage, and p53 expression. Our cellular model provided a new platform to identify dietary components, at non-cytotoxic levels, capable of effectively intervening in chronic breast cell carcinogenesis induced by cumulative exposures to low doses of environmental carcinogens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1331. doi:10.1158/1538-7445.AM2011-1331