Abstract 1234: Tamoxifen synergizes cytotoxic activity of 4-(E)-{(4-hydroxyphenylimino)-methylbenzene, 1,2-diol} (HPIMBD), a novel resveratrol analogue against breast cancer cells

Abstract

Abstract Tamoxifen is currently the first line of therapy against estrogen receptor (ER)-positive breast cancers. Prolonged treatment with tamoxifen has been associated with the development of resistant tumor phenotypes. Moreover, this treatment strategy is ineffective against ER-negative breast cancers. In this study, we have investigated the role of 4-(E)-{(4-hydroxyphenylimino)-methylbenzene, 1,2-diol} (HPIMBD), a novel analog of resveratrol, either alone or in combination with tamoxifen on the growth inhibition of breast cancer cells. Breast cancer cell lines MCF-7, T47D, MDA-MB-231 and MDA-MB-468 as well as non-neoplastic breast epithelial cell lines MCF-10A, MCF-10F and HMEC were treated with different doses of HPIMBD or a combination of tamoxifen (2µM) and HPIMBD (at its IC50 dose). Cell proliferation was determined by MTT assays. No effect on cell proliferation was observed upon treatment of non-neoplastic breast cells with HPIMBD. A dose dependent growth inhibition was demonstrated upon treatment of breast cancer cells with HPIMBD. IC50 values of HPIMBD were determined. Tamoxifen at a dose of 2µM showed no effect on the growth of breast cancer or non-neoplastic breast epithelial cell lines. However, a significant increase in inhibition of cellular proliferation of breast cancer cells was demonstrated when tamoxifen (2µM) was used in combination with HPIMBD at its IC50 dose. To investigate the mechanism of inhibition, autophagy markers, beclin-1 and LC3B were quantified by Western blot analyses. The combination treatment significantly increased the expression of autophagy marker beclin-1 and the cleavage of LC3BI to LC3BII. Cell cycle analysis showed an arrest in the S-phase by HPIMBD and G0/G1-phase by tamoxifen. Our studies suggest that a combination of tamoxifen and HPIMBD synergistically inhibit the proliferation of breast cancer cells. Autophagy and cell cycle arrest appear to be the primary mechanisms of inhibition by the combination treatment. Citation Format: Amruta Mukund Ronghe, Anwesha Chatterjee, Fatma Abdalla, Hari K. Bhat. Tamoxifen synergizes cytotoxic activity of 4-(E)-{(4-hydroxyphenylimino)-methylbenzene, 1,2-diol} (HPIMBD), a novel resveratrol analogue against breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1234. doi:10.1158/1538-7445.AM2014-1234