Abstract 2577: ARSHA, a novel analog of resveratrol inhibits proliferation of breast cancer cells by modulating expressions of ERα and ERβ.

Abstract

Abstract Epidemiologic evidence suggests that diets rich in phytoestrogens are associated with a reduced risk of breast cancer. Resveratrol, a bioflavonoid found naturally in grapes, has been very effective as an antiproliferative agent in vitro. However, its poor bioavailability and rapid metabolism limits its use as a preferred anticancer agent. The problem of poor bioavailability of resveratrol can be solved by the synthesis of its analogs with appropriate chemical modifications that would enhance the stability and anticancer potency of resveratrol. To achieve this objective, we have synthesized a library of resveratrol analogs that resemble the basic skeleton of resveratrol but have structural modifications. These novel analogs were screened for their potential to inhibit growth of breast cancer cells. One analog, namely, ARSHA showed better potential and selectivity in inhibiting the proliferation of breast cancer cells. Our next goal was to identify the mechanism by which ARSHA specifically inhibits the growth of breast cancer cells. Estrogen receptor (ER) expressing cell lines MCF-7 and T47D, and ER negative cell line MDA-MB-231 as well as ERβ-transfected cell line MDA-MB-231 were treated with 50μM doses of ARSHA for upto 72 hours. mRNA and protein was isolated from respective cell lines. Real-time PCR and western blot analyses were performed. ARSHA significantly induced the expression of ERβ (∼3-fold) and inhibited the expression of ERα (0.2-fold) compared to vehicle treated controls. Taken together, our findings indicate that novel resveratrol analog ARSHA may inhibit the proliferation of breast cancer cell lines by inhibiting the expression of ERα and inducing the expression of ERβ. Estrogen receptor α acts as a mediator of proliferation while ERβ acts as an inhibitor of estrogen signaling. Citation Format: Amruta M. Ronghe, Anwesha Chatterjee, Bhupendra Singh, Subhash B. Padhye, Hari K. Bhat. ARSHA, a novel analog of resveratrol inhibits proliferation of breast cancer cells by modulating expressions of ERα and ERβ. [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 2577. doi:10.1158/1538-7445.AM2013-2577