Tumor Biology

, Volume 36, Issue 2, pp 769–777 | Cite as

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

  • Rong Hu
  • Ying Yang
  • Zhuogang Liu
  • Huinan Jiang
  • Ke Zhu
  • Jia Li
  • Wenhui Xu
Research Article

Abstract

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.

Keywords

TRAIL Death receptor XIAP Leukemia Apoptosis 

Notes

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Rong Hu
    • 1
  • Ying Yang
    • 1
  • Zhuogang Liu
    • 1
  • Huinan Jiang
    • 1
  • Ke Zhu
    • 1
  • Jia Li
    • 1
  • Wenhui Xu
    • 1
  1. 1.Department of Hematology, Shengjing HospitalChina Medical UniversityShenyangChina

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