Abstract 3452: Role of P-glycoprotein in carcinogenesis

Abstract

Abstract Cancer accounts for nearly one-quarter of deaths in the United States, exceeded only by heart diseases. Polycyclic aromatic hydrocarbons (PAHs) are commonly found in our environment and appear to be carcinogenic by genotoxic mechanisms. Several studies show that over-expression of P-glycoprotein (Pg-p, coded by mdr1) is associated with the development of various cancers. High expression of the mdr1 gene has been reported in many human cancers such as in breast, liver, colon, kidney and brain. Many molecular and cellular studies have revealed the ability of dietary phytochemicals in vegetables and fruits to reduce the risk of cancer. The abundant and inexpensive dietary phytochemicals are being explored as Pg-p modulators in cancer chemoprevention and chemotherapy. In the present study, we investigated the role of P-gp in cancer development. We also studied whether the inhibition of P-gp function could reduce the development of cancer. The wild type (C57BL/6J) mice were exposed to the environmental PAH, 7, 12-dimethylbenz(a)anthracene (DMBA) and dietary phytochemicals, alone and in combination. The hepatic and mammary gene expressions of P-gp, Pregnane X receptor (PXR), and CYP3A11 were analyzed. The environmental PAHs induced hepatic and mammary expressions of P-gp and associated genes in mice, compared to controls. Administration of dietary phytochemicals inhibited the P-gp expression significantly. Induction of specific DNA adducts were also observed in hepatic and mammary tissues of mice treated with PAHs and phytochemicals. These studies show a potential for development of dietary phytochemicals as Pg-p modulators in chemoprevention and chemotherapy of human cancers. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 3452.