FPTB, a novel CA-4 derivative, induces cell apoptosis of human chondrosarcoma cells through mitochondrial dysfunction and endoplasmic reticulum stress pathways

Ju Fang Liu, Yi Chin Fong, Kai Wei Chang, Sheng Chu Kuo, Chih Shiang Chang, Chih Hsin Tang

研究成果: 雜誌貢獻文章同行評審

17 引文 斯高帕斯(Scopus)

摘要

Chondrosarcoma is a malignant primary bone tumor that responds poorly to both chemotherapy and radiation therapy. The aim of this study was to elucidate the mechanism of the novel Combretastatin A-4 derivative, 2-(furanyl)-5- (pyrrolidinyl)-1-(3,4,5-trimethoxybenzyl)benzoimidazole (FPTB)-induced human chondrosarcoma cells apoptosis. FPTB induced cell apoptosis in human chondrosarcoma cell line but not primary chondrocytes. FPTB induced up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL and dysfunction of mitochondria in chondrosarcoma. FPTB also triggered endoplasmic reticulum (ER) stress, as indicated by changes in cytosol-calcium levels. We found that FPTB increased glucose-regulated proteins (GRP)78 but not GRP94 expression. In addition, treatment of cells with FPTB induced calpain expression and activity. Transfection of cells with GRP78 or calpain siRNA reduced FPTB-mediated cell apoptosis. Therefore, FPTB-induced apoptosis in chondrosarcoma cells through the mitochondria dysfunction and involves caspase-9 and caspase-3-mediated mechanism. FPTB also induced cell death mediated by increasing ER stress, GPR78 activation, and Ca2+ release, which subsequently triggers calpain, caspase-12 and caspase-3 activity, resulting in apoptosis.
原文英語
頁(從 - 到)453-462
頁數10
期刊Journal of Cellular Biochemistry
112
發行號2
DOIs
出版狀態已發佈 - 二月 1 2011

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 細胞生物學

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