The flavonoid casticin enhances TRAIL-induced apoptosis of colon cancer cells through endoplasmic reticulum stress-mediated up-regulation of DR5  

黄酮类化合物紫花牡荆素通过内质网应激上调死亡受体5促进TRAIL诱导的结肠癌细胞凋亡(英文)

作　　者：Sanyuan Tang Guangjin Yuan Zhengyang Yu Leilan Yin Hao Jiang 

机构地区：[1]Department of Medical Oncology,The First Affiliated Hospital of Nanhua University [2]Cancer Hospital of Chongqing Qianjiang National Hospital

出　　处：《The Chinese-German Journal of Clinical Oncology》2013年第6期279-284,共6页中德临床肿瘤学杂志（英文版）

摘　　要：Objective： The aim of this study was to explore the mechanisms by which the flavonoid casticin enhances tumor necrosis factor-related apoptosis-inducing ligand （TRAIL）-induced apoptosis in colon cancer cells. Methods： Human colon cancer HT-29 cells were treated with TRAIL or casticin. Cytotoxicity was examined by MTT assay, and apoptosis determined by morphological observation and flow cytometric analysis. Death receptor 5 （DRS）, DR4, and endoplasmic reticulum （ER） stress response markers, including glucose regulating protein 78 （GRP78）, activating transcription factor 4 （ATF4） and CHOP （CCAAT/enhancer binding protein homologous protein）, were examined with western blot. Small interfering RNA （siRNA） transfection was employed to knock down CHOP. Results： HT-29 cells were resistance to TRAIL-induced apoptosis, but casticin, at subtoxic concentrations, potentiated HT-29 cells to TRAIL-induced apoptosis. Casticin up-regulated the expression of DR5 time-and dose-dependent manners, but had no effect on the expression of DR4. Also, casticin increased the levels of ER stress response markers （GRP78, ATF4 and CHOP） in a similar way to DR5. Knockdown of CHOP by specific siRNA, or salubrinal, an ER stress inhibitor, abolished the up-regulation of DR5 and enhancement of TRAIL-induced apoptosis by casticin. Conclusion： Casticin enhances TRAIL-induced apoptosis of colon cancer cells by ER stress-mediated up-regulation of DR5.

关 键 词：CASTICIN tumor necrosis factor-related apoptosis-inducing ligand （TRAIL） apoptosis endoplasmic reticulum（ER） stress death receptor 5 （DR5） colon cancer 

分 类 号：R285.5[医药卫生—中药学]