The XIAP inhibitor Embelin enhances TRAIL-induced apoptosis in human leukemia cells by DR4 and DR5 upregulation

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• 作者：Rong Hu (1)
  Ying Yang (1)
  Zhuogang Liu (1)
  Huinan Jiang (1)
  Ke Zhu (1)
  Jia Li (1)
  Wenhui Xu (1)
  
  1. Department of Hematology ; Shengjing Hospital ; China Medical University ; Shenyang ; 110004 ; Liaoning ; China
  
• 关键词：TRAIL ; Death receptor ; XIAP ; Leukemia ; Apoptosis
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：36
• 期：2
• 页码：769-777
• 全文大小：1,158 KB
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• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

The present study was designed to explore the effects of low-toxicity Embelin on TRAIL-induced apoptosis and its possible mechanism in human leukemia cells. Our study showed that low-toxicity Embelin enhanced TRAIL-induced apoptosis through DR4 and DR5 upregulation and caspase activation in HL-60 cells. Pan-caspase inhibitor Z-VAD-FMK inhibited cell apoptosis induced by TRAIL alone or combined with low-toxicity Embelin, which indicated the cytotoxic effect is mediated by caspase-dependent apoptosis. Although Embelin is an X chromosome-linked inhibitor-of-apoptosis protein (XIAP) inhibitor, an XIAP independent effect on cell death was detected in HL-60 cells exposed to low-toxicity Embelin and TRAIL. Low-toxicity Embelin upregulated DR4 and DR5 expression to enhance TRAIL-induced apoptosis. The sensitizing effects of Embelin on TRAIL-induced apoptosis were markedly attenuated when DR4/DR5 was knocked down. These data suggested that low-toxicity Embelin enhanced TRAIL-induced cell apoptosis through DR4 and DR5 upregulation, indicating that combination of low-toxicity Embelin and TRAIL may become as a potential antileukemia strategy.