Abstract 2128: Salvianolic acid B inhibits both ER-α +/- breast cancer cell growth in vivo and in vitro

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL PURPOSE: Estrogen receptor α negative (ER-α/-) breast cancer cells are found to respond poorly to chemotherapeutic agents. Salvianolic acid B (Sal-B) is an active depside compound isolated from Salvia miltiorrhiza Bge, which is a well-known Chinese medicine that has been widely used to treat various disorders including cancers. In this study, we evaluated the anti-cancer activity of Sal-B leading to ceramide-mediated apoptosis in ER-α + and ER-α – cancer cell lines. DESIGN METHODS: Using MCF-7-luc (ER-α/+) and MDA-MB-231-luc (ER-α/-) human breast cancer cell lines as a test model, cell-based bioluminescence assay and colony assay for cell viability, Western Blot analysis for ER-α and apoptosis-related proteins expression, flow cytometry analysis for cell cycle, and tumor xenografts were performed. RESULTS: Significant decreased cell viabilities (p<0.05) were observed in Sal-B treated ER-α + and ER-α – cells. The expression of anti-apoptotic proteins (Bcl-2, Bcl-XL and surviving) and ceramide metabolism enzymes (GCS and GM3 synthase) all markedly decreased. Sal-B treatment suppressed cell cycle related protein expression, such as cyclin A and B. Further analysis using flow cytometry confirmed these observations. The tumor size was significantly lower in Sal-B treated MDA-MB-231-luc cells transplanted mice group compared to untreated control group and doxorubicin treated group. CONCLUSION: Sal-B effectively inhibits the growth of cultured ER-α +/- cell lines and MDA-MB-231-luc tumor xenografts. In addition, Sal-B is able to modulate ceramide-mediated apoptosis by inhibiting ceramide metabolic enzymes (GCS and GM3 synthase). Thus, Sal-B has high potential to be a new therapeutic strategy to improve ER-α/- cancer treatment. Research supported in part by grants P20 CA118770 and U54 CA091431 from NCI/NIH and 2G12 RR003048 from the RCMI Program/NCRR/NIH. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2128. doi:10.1158/1538-7445.AM2011-2128