A novel curcumin derivative increases the cytotoxicity of raloxifene in estrogen receptor-negative breast cancer cell lines.

摘要: There is a need for new, safe and efficacious drug therapies the treatment of estrogen receptor (ER)-negative breast cancers. Raloxifene 2nd generation curcumin derivative 2,6-bis(pyridin-4-ylmethylene)-cyclohexanone (RL91) have been shown to inhibit growth ER-negative cancer cells in vitro in vivo. We investigated whether RL91 could enhance growth-suppressive effects mediated by raloxifene in MDA-MB-231, MDA-MB-468, Hs578t SkBr3 human cell lines. The cytotoxicity was consistent across lines but more potent. EC50 values were 1.2-2 µM while 9.6-11.2 µM. When treated with (15 µM), (1 µM) or combination two 6-72 h, consistently elicited significantly greater compared all other treatments. In caused undergo G1 arrest raloxifene. apoptosis synergistically induced treatment, as both flow cytometery cleaved caspase-3. Furthermore, stress kinase p38 increased EFGR isoforms decreased + RL91. anti-angiogenic anti-metastatic potential not RL91, MDA-MB-231 migration invasion well endothelial tube formation HUVEC different between (10 µM) Thus, our findings provide evidence that increases ability suppress increasing number apoptotic cells. broad effect this range indicates should be explored further order find therapy cancer.