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

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Tumor Biology

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.

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Authors and Affiliations

  1. Department of Hematology, Shengjing Hospital, China Medical University, Shenyang, 110004, China

    Rong Hu, Jia Li, Zhuogang Liu, Miao Miao & Kun Yao

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  1. Rong Hu
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  2. Jia Li
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  3. Zhuogang Liu
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  4. Miao Miao
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  5. Kun Yao
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Correspondence to Zhuogang Liu.

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Hu, R., Li, J., Liu, Z. et al. GDC-0152 induces apoptosis through down-regulation of IAPs in human leukemia cells and inhibition of PI3K/Akt signaling pathway. Tumor Biol. 36, 577–584 (2015). https://doi.org/10.1007/s13277-014-2648-8

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  • DOI: https://doi.org/10.1007/s13277-014-2648-8

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