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Tumor Biology

, Volume 36, Issue 2, pp 577–584 | Cite as

GDC-0152 induces apoptosis through down-regulation of IAPs in human leukemia cells and inhibition of PI3K/Akt signaling pathway

  • Rong Hu
  • Jia Li
  • Zhuogang Liu
  • Miao Miao
  • Kun Yao
Research Article

Abstract

The inhibitor of apoptosis proteins (IAPs) is closely related to leukemia apoptosis. The present study was undertaken to determine the molecular mechanisms by which GDC-0152, an IAP inhibitor, induces apoptosis in human leukemia cells (K562 and HL60 cells). GDC-0152 inhibited the proliferation of K562 and HL60 cells in a dose- and time-dependent manner, which was largely attributed to intrinsic apoptosis. GDC-0152 down-regulated the IAPs including X-linked inhibitor of apoptosis protein (XIAP), cellular inhibitor of apoptosis protein-1 (cIAP1), and cellular inhibitor of apoptosis protein-2 (cIAP2) expression and induced the activation of caspase-9 and caspase-3. GDC-0152-induced cell proliferation inhibition in K562 cells was prevented by pan-caspase inhibitor. GDC-0152 also inhibited PI3K and Akt expression in K562 and HL60 cells. Taken together, these findings suggest that GDC-0152 results in human leukemia apoptosis through caspase-dependent mechanisms involving down-regulation of IAPs and inhibition of PI3K/Akt signaling.

Keywords

GDC-0152 IAPs Leukemia PI3K/Akt signaling pathway 

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
  • Jia Li
    • 1
  • Zhuogang Liu
    • 1
  • Miao Miao
    • 1
  • Kun Yao
    • 1
  1. 1.Department of Hematology, Shengjing HospitalChina Medical UniversityShenyangChina

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