a synergistic antiproliferation effect of curcumin and docosahexaenoic acid in sk-br-3 breast cancer cells unique signaling not explained by the effects of either compound alone姜黄素和二十二碳六烯酸的协同抗效应sk-br-3乳腺癌细胞独特的信号不是用的影响来解释化合物.pdfVIP

Altenburg et al. BMC Cancer 2011, 11:149 /1471-2407/11/149 RESEARCH ARTICLE Open Access A synergistic antiproliferation effect of curcumin and docosahexaenoic acid in SK-BR-3 breast cancer cells: unique signaling not explained by the effects of either compound alone 1 2 1 1 1 1 Jeffrey D Altenburg , Andrew A Bieberich , Colin Terry , Kevin A Harvey , Justin F VanHorn , Zhidong Xu , V Jo Davisson2 and Rafat A Siddiqui1,3,4* Abstract Background: Breast cancer is a collection of diseases in which molecular phenotypes can act as both indicators and mediators of therapeutic strategy. Therefore, candidate therapeutics must be assessed in the context of multiple cell lines with known molecular phenotypes. Docosahexaenoic acid (DHA) and curcumin (CCM) are dietary compounds known to antagonize breast cancer cell proliferation. We report that these compounds in combination exert a variable antiproliferative effect across multiple breast cell lines, which is synergistic in SK-BR-3 cells and triggers cell signaling events not predicted by the activity of either compound alone. Methods: Dose response curves for CCM and DHA were generated for five breast cell lines. Effects of the DHA+ CCM combination on cell proliferation were evaluated using varying concentrations, at a fixed ratio, of CCM and DHA based on their individual ED50. Detection of synergy was performed using nonlinear regression of a sigmoid dose response model and Combination Index approaches. Cell molecular network responses were investigated through whole genome microarray analysis of transcript level changes. Gene expression results were validated by RT-PCR, and western blot analysis was performed for potential signaling mediators. Cellular curcu