Abstract 131: Mechanisms by which 2,3’, 4,5’ tetramethoxystilbene (TMS), a resveratrol derivative, induces death in breast cancer cells

We have examined a non-toxic pro-apoptotic agent, TMS (2, 3’,4, 5’ tetramethoxystilbene), which belongs to the Resveratrol family of stilbenes. To learn about the mechanism by which TMS achieved its effects we carried out microarray analysis and found that TMS treatment increased tubulin genes as well as stress response and pro-apoptotic genes. Fractionation studies uncovered that TMS treatment causes cleavage of Bax from the p21 form to a truncated p18 form. Co-localization analysis of immunofluorescent studies showed that Bax moved from the cytosol to the mitochondria. In addition, the pro-apoptotic proteins Noxa and Bim (EL, L, and S) were increased upon TMS treatment. Breast cancer cell lines reduced for Bax, Bim and Noxa are compromised for TMS-mediated cell death. Transmission electron microscopy revealed evidence of nuclear condensation, formation of apoptotic bodies and DAPI staining showed evidence of DNA fragmentation. TMS treatment was able to induce both caspase-independent and caspase-dependent death via the intrinsic death pathway. 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 131.