S1 kills MCF-7/ADR cells more than MCF-7 cells: A protective mechanism of endoplasmic reticulum stress

详细信息    查看全文

• 作者：Ting Song ; Furong Liang ; Zhichao Zhang ; Yubo Liu ; Hongkun Sheng ; Mingzhou Xie
• 关键词：MCF-7/ADR ; ER stress ; BH3 mimetic ; Apoptosis ; PBcl-2
• 刊名：Biomedicine and Pharmacotherapy
• 出版年：October, 2013
• 年：2013
• 卷：67
• 期：8
• 页码：731-736
• 全文大小：927 K

文摘

Drug resistance in chemotherapy for breast cancer is associated with high levels of P-glycoprotein (P-gp) as well as endoplasmic reticulum (ER) stress. In this paper, we aimed to evaluate the efficacy of a pan-BH3 mimetic S1 on drug-resistant MCF-7/ADR cells, and the roles of S1-induced ER stress in cell death. S1 exhibited greater and faster mitochondrial apoptosis in MCF-7/ADR cells than in MCF-7 cells. We demonstrated by Bax/Bak activation and cyrochrome c release that the p-glycprotein had little influence on S1 entering cells and hitting its targets in MCF-7/ADR cells. An IRE1-mediated ER stress response followed by c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) activation was specifically induced by S1 in MCF-7 cells, but not in MCF-7/ADR cells. Coimmunoprecipitation and western blotting analysis determined that ER stress played a protective role in S1-induced apoptosis by triggering Bcl-2 phosphorylation, which grabbed more pro-apoptotic proteins. The synergism effect of ERK inhibitor PD98059 with S1 confirmed the protective role of ER stress. Defective ER stress in MCF-7/ADR cells confers the more sensitivity toward S1.