Wang Kai-Lee, Hsia Shih-Min, Yeh Jiun-Yih, Cheng Shao-Chi, Wang Paulus S, Wang Shyi-Wu
Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China ; The Center of General Education, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan, Republic of China.
PLoS One. 2013 Jun 26;8(6):e67297. doi: 10.1371/journal.pone.0067297. Print 2013.
Endocrine sensitivity, assessed by the expression of estrogen receptor (ER), has long been the predict factor to guide therapeutic decisions. Tamoxifen has been the most successful hormonal treatment in endocrine-sensitive breast cancer. However, in estrogen-insensitive cancer tamoxifen showed less effectiveness than in estrogen-sensitive cancer. It is interesting to develop new drugs against both hormone-sensitive and insensitive tumor. In this present study we examined anticancer effects of evodiamine extracted from the Chinese herb, Evodiae fructus, in estrogen-dependent and -independent human breast cancer cells, MCF-7 and MDA-MB-231 cells, respectively. Evodiamine inhibited the proliferation of MCF-7 and MDA-MB-231 cells in a concentration-dependent manner with concentration of 1×10(-6) and 1×10(-5) M. Evodiamine also induced apoptosis via up-regulation of caspase 7 activation, PARP cleavage (Bik and Bax expression). The expression of ER α and β in protein and mRNA levels was down-regulated by evodiamine according to data from immunoblotting and RT-PCR analysis. Overall, our results indicate that evodiamine mediates degradation of ER and induces caspase-dependent pathway leading to inhibit proliferation of breast cancer cell lines. It suggests that evodiamine may in part mediate through ER-inhibitory pathway to inhibit breast cancer cell proliferation.
通过雌激素受体（ER）表达评估的内分泌敏感性长期以来一直是指导治疗决策的预测因素。他莫昔芬一直是内分泌敏感型乳腺癌中最成功的激素治疗药物。然而，在雌激素不敏感型癌症中，他莫昔芬的疗效低于雌激素敏感型癌症。研发针对激素敏感型和不敏感型肿瘤的新药很有意义。在本研究中，我们分别检测了从中药吴茱萸中提取的吴茱萸碱对雌激素依赖型和非依赖型人乳腺癌细胞MCF-7和MDA-MB-231细胞的抗癌作用。吴茱萸碱以浓度依赖方式抑制MCF-7和MDA-MB-231细胞的增殖，浓度分别为1×10(-6)和1×10(-5)M。吴茱萸碱还通过上调半胱天冬酶7激活、PARP裂解（Bik和Bax表达）诱导细胞凋亡。根据免疫印迹和RT-PCR分析数据，吴茱萸碱下调了ERα和β在蛋白质和mRNA水平的表达。总体而言，我们的结果表明，吴茱萸碱介导ER降解并诱导半胱天冬酶依赖性途径，从而抑制乳腺癌细胞系的增殖。这表明吴茱萸碱可能部分通过ER抑制途径介导抑制乳腺癌细胞增殖。
