Abstract 4868: Dietary resveratrol promotes breast cancer progression in immunocompromised mice.

Abstract

Abstract Resveratrol, a polyphenol from grapes and red wine has been widely studied due to its beneficial effects against cardiovascular diseases and cancer. However, our group and others have provided evidence for a dual cancer promoting or inhibitory role for resveratrol in breast cancer, dependent on the concentration. Moreover, much of the reported inhibitory effects of resveratrol are from studies with high non-physiological concentrations. Herein, we investigated the effects of low (0.5 and 5 mg/kg body weight) and moderate concentrations (50 mg/kg body weight) of resveratrol on mammary tumor growth, using immunocompromised mice. Our findings suggest promotion of mammary tumor growth and metastasis by resveratrol at all concentrations tested in tumors derived from the low metastatic estrogen receptor (ER)α(-), ERβ(+) MDA-MB-231 and the highly metastatic ER(-) MDA-MB-435 cancer cell lines. Additionally, the activity of the migration/invasion regulator Rac, which we have previously shown to be regulated by resveratrol in vitro, was measured in tumors from resveratrol treated mice. Our results show a significant induction of tumoral Rac activity and a trend in increased expression of the Rac downstream effector PAK1, Akt, and jun kinase (JNK) following resveratrol treatment. Taken together, our findings implicate low concentrations of resveratrol in potential promotion of breast cancer. Because of this dual role of resveratrol on cancer progression, measuring circulating plasma levels of resveratrol becomes critical and could be used as a prognostic tool for resveratrol's responsiveness. Since, detection and quantification of low levels of resveratrol is limited by the sensitivity of existing methodologies, we developed a rapid UPLC-tandem MS method to quantify resveratrol from plasma. This method requires minimal sample preparation and allows the quantification of resveratrol in mouse plasma at lower levels and shorter retention times than those previously reported by similar methodologies. This study was supported by DoD/BCRP W81XWH-08-1-0258 to LCP, DoD/BCRP W81XWH-07-1-0330 to SD, the UCC Pilot Project Program, the UCC Postdoctoral Program sponsored by the PR Science, Technology and Research Trust, and the Title V PPOHA grant number PO31M105050 from U.S. Department of Education to UCC. Citation Format: Linette Castillo-Pichardo, Luis A. Cubano, José F. Rodríguez-Orengo, Suranganie Dharmawardhane. Dietary resveratrol promotes breast cancer progression in immunocompromised mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4868. doi:10.1158/1538-7445.AM2013-4868