Reactive oxygen species-mediated endoplasmic reticulum stress and mitochondrial dysfunction contribute to cirsimaritin-induced apoptosis in human gallbladder carcinoma GBC-SD cells
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- 作者：Zhiwei Quan ; Jun Gu ; Ping Dong ; Jianhua Lu ; Xiangsong Wu ; Wenguang Wu ; Xiaozhou Fei ; Songgang Li ; Yong Wang ; Jianwei Wang ; Yingbin Liu
- 关键词：Gallbladder carcinoma ; Cirsimaritin ; Apoptosis ; Reactive oxygen species ; Endoplasmic reticulum stress
- 刊名：Cancer Letters
- 出版年：2010
- 出版时间：28 September 2010
- 年：2010
- 卷：295
- 期：2
- 页码：252-259
- 全文大小：794 K
文摘
In this study, the anticancer effect of cirsimaritin, a natural flavonoid, against human gallbladder carcinoma cell line GBC-SD and the underlying mechanisms were investigated. Cirsimaritin inhibited the growth of tumor cells and induced mitochondrial apoptosis in GBC-SD cells. In addition, cirsimaritin triggered endoplasmic reticulum (ER) stress and down-regulated the phosphorylation of Akt, while knock-down of CHOP dramatically abrogated the inactivation of Akt and reversed the pro-apoptotic effect of cirsimaritin. Furthermore, cirsimaritin provoked the generation of reactive oxygen species in GBC-SD cells, while the antioxidant N-acetyl cysteine almost completely blocked the activation of ER stress and apoptosis, suggesting cirsimaritin-induced reactive oxygen species is an early event that triggers ER stress mitochondrial apoptotic pathways in GBC-SD cells.