Abstract 4376: Biological, biochemical, and molecular targets for dietary catechin-induced suppression of breast cell chronic carcinogenesis

Abstract

Abstract This study is to identify biological, biochemical, and molecular targets for dietary catechins in early prevention of breast cell carcinogenesis induced chronically by environmental carcinogens. Breast cell carcinogenesis is a multiyear, multistep, and multipath disease process and is the most common type of cancer among women in northern America and northern Europe. Epidemiologic and experimental evidence suggests that dietary constituents in fruits and vegetables prevent human cancers; dietary prevention is a cost-efficient strategy to reduce the risk of this disease. However, the mechanisms for dietary prevention of cellular carcinogenesis induced by chronic exposure to environmental carcinogens remain to be elucidated. To identify dietary components for prevention of chronic human breast cell carcinogenesis, we studied biological, biochemical, and molecular target endpoints that were induced by low doses of carcinogens and suppressed by dietary catechins. Immortalized, non-cancerous human breast epithelial MCF10A cells were repeatedly exposed to carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and/or benzo[α]pyrene (B[α]P), each at picomolar concentrations, to induce cancer-associated biological, biochemical, and molecular properties in cells. We then used these changes as target endpoints to reveal the activity of various dietary catechins in suppression of NNK- and B[α]P-induced cellular carcinogenesis. We identified that cells acquiring the biological properties of reduced dependence on growth factors, anchorage-independent growth, and acinar-conformational disruption were reduced by treatment with dietary catechins. We identified that hydroxysteroid (11-beta) dehydrogenase 2 (HSD11B2) played a novel role in NNK- and B[α]P-induced cellular carcinogenesis, and its expression acted as a molecular target endpoint in catechin-induced suppression of cellular carcinogenesis. The ability of catechins to reduce gene expression of cytochrome P450 enzymes CYP1A1 and CYP1B1, which can bioactivate NNK and B[α]P, may be involved in the preventive mechanism for catechins in suppression of cellular carcinogenesis. Our model system with biological, biochemical, and molecular target endpoints verified the value of dietary catechins for prevention of human breast cell carcinogenesis induced by repeated exposures to low doses of multiple environmental carcinogens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4376.