Abstract 5366: NAD(P)H-Quinone oxidoreductase (NQO1): Potential role in the prevention of estrogen-induced breast cancer

Abstract

Abstract The importance of estrogens in the etiology of breast cancer is widely recognized. However, the exact mechanisms underlying the initiation and progression of estrogen-related cancers are not clear. Literature evidence and our studies strongly support the role of estrogen metabolism-mediated oxidative stress in estrogen-induced breast carcinogenesis. The objective of the current study was to characterize the role of NQO1 in the prevention of estrogen-induced mammary tumorigenesis by antioxidants vitamin C or butylated hydroxyanisole (BHA). NQO1 converts 17β-estradiol (E2)-quinones back to E2-catechols, thus making E2-quinones unavailable for oxidant damage. Female ACI rats were treated with E2 (3 mg); vitamin C (1% in drinking water); E2 + vitamin C; BHA (0.7% in diet); and E2 + BHA for up to 8 months. The female ACI rat is an established animal model to study the mechanisms of E2-induced breast cancer. The protein isolated from breast tissue and breast tumor tissue of rats treated with E2 and antioxidants was analyzed for NQO1 expression. NQO1 was suppressed in E2-exposed mammary tissue after treatment of rats with E2 for 8 months and in mammary tumors. This suppression was overcome by co-treatment of rats with E2 and vitamin C or BHA. Co-treatment of rats with E2 and vitamin C resulted in a 4-fold induction of NQO1 compared to control mammary tissue. Similarly, co-treatment of rats with E2 and BHA induced NQO1 4.4-fold compared to control mammary tissue. There was no change in NQO1 expression during early time points of E2 exposure (7 and 15 days). The up-regulation of NQO1 by vitamin C or BHA was evident after 4 months of treatment. There was no effect of BHA or vitamin C treatment on NQO1 expression on other non-target organs like liver, lung and heart except kidney. These studies suggest a protective role of NQO1 in E2-induced breast carcinogenesis. NQO1 may thus have a great potential in the development of therapeutic strategies for the prevention of estrogen-induced neoplasia. 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 5366.