Abstract
BackgroundCurcumin, a natural compound derived from the turmeric rhizome Curcuma longa Linn, has anticancer and chemoresistance reduction biological activities. We evaluated the efficacy of curcumin in sensitizing chemotherapy drugs through regulation of Bcl-2-mediated apoptosis in breast cancer stem-like cells (BCSCs).MethodsCell survival was measured using MTT assay. Apoptosis-related proteins were observed using western blot analysis. Apoptosis was detected with flow cytometric analysis and by Hoechst 33258 staining. The mitochondrial membrane potential was observed with flow cytometric analysis.ResultsThe ability of BCSCs to propagate decreased gradually along the passages and was completely lost at the fifth passage [0.1 μmol/L mitomycin C (MMC) with 5 μmol/L curcumin in MCF-7 and 0.5 μmol/L MMC with 5 μmol/L curcumin in MDA-MB-231 cells]. Curcumin combined with MMC treatment significantly decreased the levels of antiapoptotic Bcl-2 and Bcl-w expression, increased the levels of proapoptotic Bax, Bak, Bad, Bik, and Bim expression, and activated caspase-3 and caspase-9 in MCF-7 BCSCs. In the presence of Bcl-2 siRNA, the apoptosis rate increased by 15% in cells treated with curcumin and MMC. The mitochondrial membrane potential decreased by approximately 20% in MCF-7 BCSCs undergoing the combination treatment of curcumin and MMC. The combination-induced decrease in Bcl-2 was regulated by the presence of the Wnt-specific inhibitor PFK115-584 and PI3k inhibitor LY294002.ConclusionsOur study indicates that curcumin might represent a novel therapeutic agent for treating breast cancer chemoresistance induced by MMC.
Highlights
Curcumin significantly enhances the capability of MMC to reduce the self‐renewal of stem‐like breast cancer cells In a previous study, we found that, with 5 μmol/L curcumin, MMC reduced mammosphere-forming efficiency (MSFE) by 50% at 0.1 μmol/L in MCF-7 cells and 0.5 μmol/L in MDA-MB-231 cells, representing 5and 15-fold decreases in the concentration required to achieve such a reduction, respectively
We investigated the effects of MMC on the self-renewal of MDA-MB-231 and MCF-7 cells with or without curcumin
On the basis of the formation of mammosphere structures, breast cancer stem-like cells (BCSCs) derived from MCF-7 and MDAMB-231 cells were able to propagate in media containing 0.1 μmol/L MMC with 5 μmol/L curcumin and 0.5 μmol/L MMC with 5 μmol/L curcumin, respectively
Summary
More than 1.3 million women worldwide are diagnosed every year [1]. Chemotherapy, surgery, and radiation are available for treatment of the primary tumor in breast cancer. Chemoresistance remains a major obstacle to the treatment of breast cancer, and leads to poor prognoses [2]. Resistance occurs at the beginning of chemotherapy and following successful chemotherapy. A natural compound derived from the turmeric rhizome Curcuma longa Linn, has anticancer and chemoresistance reduction biological activities. We evaluated the efficacy of curcumin in sensitizing chemother‐ apy drugs through regulation of Bcl-2-mediated apoptosis in breast cancer stem-like cells (BCSCs)
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