Chung Seyung S, Vadgama Jaydutt V
Division of Cancer Research and Training, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, U.S.A.
Division of Cancer Research and Training, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, U.S.A. Jonson Comprehensive Cancer Center, Los Angeles, CA, U.S.A. UCLA Department of Medicine, Los Angeles, CA, U.S.A.
Anticancer Res. 2015 Jan;35(1):39-46.
BACKGROUND/AIM: The cancer stem cell (CSC) model postulates the existence of a small proportion of cancer cells capable of sustaining tumor formation, self-renewal and differentiation. Signal Transducer and Activator of Transcription 3 (STAT3) signaling is known to be selectively activated in breast CSC populations. However, it is yet to be determined which molecular mechanisms regulate STAT3 signaling in CSCs and what chemopreventive agents are effective for suppressing CSC growth. The aim of this study was to examine the potential efficacy of curcumin and epigallocatechin gallate (EGCG) against CSC and to uncover the molecular mechanisms of their anticancer effects.
To suppress the CSC phenotype, two breast cancer cell lines (MDA-MB-231 cells and MCF7 cells transfected with HER2) were treated with curcumin (10 μM) with or without EGCG (10 μM) for 48 h. We used tumor-sphere formation and wound-healing assays to determine CSC phenotype. To quantify CSC populations, Fluorescence-activated cell sorting profiling was monitored. STAT3 phosphorylation and interaction with Nuclear Factor-kB (NFkB) were analyzed by performing western blot and immunoprecipitation assays.
Combined curcumin and EGCG treatment reduced the cancer stem-like Cluster of differentiation 44 (CD44)-positive cell population. Western blot and immunoprecipitation analyses revealed that curcumin and EGCG specifically inhibited STAT3 phosphorylation and STAT3-NFkB interaction was retained.
This study suggests that curcumin and EGCG function as antitumor agents for suppressing breast CSCs. STAT3 and NFκB signaling pathways could serve as targets for reducing CSCs leading to novel targeted-therapy for treating breast cancer.
背景/目的：癌症干细胞（CSC）模型假定存在一小部分能够维持肿瘤形成、自我更新和分化的癌细胞。已知信号转导和转录激活因子3（STAT3）信号在乳腺CSC群体中被选择性激活。然而，尚未确定哪些分子机制调节CSC中的STAT3信号，以及哪些化学预防剂对抑制CSC生长有效。本研究的目的是研究姜黄素和表没食子儿茶素没食子酸酯（EGCG）对CSC的潜在疗效，并揭示其抗癌作用的分子机制。
为了抑制CSC表型，用姜黄素（10μM）加或不加EGCG（10μM）处理两种乳腺癌细胞系（MDA-MB-231细胞和转染HER2的MCF7细胞）48小时。我们使用肿瘤球形成和伤口愈合试验来确定CSC表型。为了量化CSC群体，监测荧光激活细胞分选分析。通过蛋白质免疫印迹和免疫沉淀试验分析STAT3磷酸化以及与核因子-κB（NFκB）的相互作用。
姜黄素和EGCG联合处理减少了癌干细胞样分化簇44（CD44）阳性细胞群体。蛋白质免疫印迹和免疫沉淀分析表明，姜黄素和EGCG特异性抑制STAT3磷酸化，并且保留了STAT3-NFκB相互作用。
本研究表明，姜黄素和EGCG作为抗肿瘤剂可抑制乳腺CSC。STAT3和NFκB信号通路可作为减少CSC的靶点，从而为治疗乳腺癌带来新的靶向治疗方法。
