Isoobtusilactone A Sensitizes Human Hepatoma Hep G2 Cells to TRAIL-Induced Apoptosis via ROS and CHOP-Mediated Up-regulation of DR5

in Sciences Citation Index(SCI), 科學引文索引資料庫(SCI)
標題Isoobtusilactone A Sensitizes Human Hepatoma Hep G2 Cells to TRAIL-Induced Apoptosis via ROS and CHOP-Mediated Up-regulation of DR5
出版類型SCI(Sciences Citation Index)
出版年度2012
AuthorsChung-Yi Chen, 陳中一, Shuenn-Jiun Yiin 尹順君, Liao Ming-Huei 徐睿良, Wei-Che Wang 王偉哲, Shan-Chun Lin 林祥中, & Chi-Liang Chern 陳志良
開始頁3533
頁數6
出版日期2012 / 1
其他編號0000
中文摘要

Hepatoma cells are relatively resistant to TRAIL. We have previously shown that isoobtusilactone A (IOA), a potent anticancer agent isolated from Cinnamomum kotoense, induced mitochondria-mediated apoptosis in hepatoma cells. Here, we report that IOA could potentiate TRAIL-induced apoptosis in Hep G2 cells. The combined treatment with IOA and TRAIL significantly induced caspase-dependent apoptosis. This correlated with the up-regulation of C/EBP homologous protein (CHOP) and death receptor 5 (DR5) protein levels. Gene silencing of the DR5 by small interfering RNA abrogated the apoptosis induced by the combined regimen of IOA and TRAIL, suggesting that the sensitization to TRAIL was mediated through DR5. By analyzing the DR5 promoter, we found that IOA induced a CHOP-dependent DR5 transactivation. DR5 expression after IOA treatment was accompanied by provoking intracellular reactive oxygen species (ROS) generation. Pretreatment with N-acetyl-L-cysteine (NAC) attenuated IOA-induced CHOP and DR5 expression and inhibited TRAIL-induced apoptosis. Taken together, our data suggested that ROS-dependent and CHOP-regulated DR5 expression played a pivotal role in the synergistic enhancement of TRAIL-induced apoptosis instigated by IOA in Hep G2 cells.

期刊名稱Journal of Agricultural and Food Chemistry
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