Abstract 2576: Novel resveratrol analog ARSHA shows higher potency for inhibiting the growth of triple negative breast cancer cells.

Abstract

Abstract Resveratrol (Res) (3, 5, 4’-trihydroxystilbene) is a well known naturally occurring polyphenol that exhibits anti-tumor activity. However, its poor bioavailability and rapid metabolism limits its use as a preferred anticancer agent. In an attempt to improve the bioavailability and anticancer potential of Res, we have synthesized five new Res analogs. We then tested the ability of these analogs to inhibit the proliferation of 5 breast cancer cell lines and 3 non-neoplastic breast epithelial cell lines and compared their inhibition potential with Res. MTT assay for cell proliferation was carried out in human breast cancer and non-neoplastic breast epithelial cell lines. The breast cancer cell lines tested were MCF-7, T47D, MDA-MB-231, MDA-MB-468 and BT-20. The non-neoplastic breast cell lines tested were MCF-10A, MCF-10F and HMLE. Of all the analogs tested, one namely ARSHA showed higher potency for inhibiting the proliferation of breast cancer cells compared to Res. Furthermore, ARSHA showed higher potency for inhibiting the growth of triple negative breast cancer cells (MDA-MB-231, MDA-MB-468 and BT-20) compared to estrogen receptor positive breast cancer cells MCF-7 and T47D. There was neither inhibition nor proliferation by ARSHA of non-neoplastic breast epithelial cell lines tested when compared to vehicle-treated controls. ARSHA induced Beclin-1 and LC3II which suggest autophagy mediated inhibition of cell growth. Beclin-1 is known to be suppressed in breast cancers and it's over expression is reported to inhibit breast cancer. Results from our studies demonstrate that Res-analog ARSHA is better than Res in inhibiting specifically breast cancer cell growth and shows higher potency for inhibiting the growth of triple negative breast cancer cells by inducing autophagy with an earlier onset for triple negative breast cancer cells. Therefore, ARSHA may be a better chemotherapeutic agent than Res against breast cancer and more specifically against triple negative breast cancer cell growth, a cancer type prevalent in minority African American population with poor prognosis. Citation Format: Anwesha Chatterjee, Amruta M. Ronghe, Bhupendra Singh, Subhash B. Padhye, Hari K. Bhat. Novel resveratrol analog ARSHA shows higher potency for inhibiting the growth of triple negative breast cancer cells. [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 2576. doi:10.1158/1538-7445.AM2013-2576