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GDC-0152-induced autophagy promotes apoptosis in HL-60 cells

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Abstract

GDC-0152 is a new type of chemical compound which can downregulate inhibitor of apoptosis protein. We previously reported that GDC-0152 induced apoptosis in HL-60 cells in a caspase-dependent manner. In this study, we have focused on GDC-0152-induced autophagy and the relationship between apoptosis and autophagy. We found that GDC-0152 can evoke autophagy flux as confirmed by the upregulation of LC3 and downregulation of p62. The conversion of LC3I to LC3II verified the existence of autophagy flux further. GDC-0152 induced autophagy through downregulating B cell lymphoma 2 and Bcl-2-interacting myosin-like coiled-coil protein, and upregulating WD-repeat domain phosphoinositide-interacting protein 1. Pretreating HL-60 cells with autophagy inhibitor Bafolimycin A1 reduced GDC-0152-induced apoptosis. However, pretreatment with caspase inhibitor Z-VAD-FMK had no effect on autophagy. Reactive oxygen species were released in GDC-0152-treated HL-60 cells but did not take part in the regulation of autophagy and apoptosis. In conclusion, our findings suggest that GDC-0152-induced autophagy can trigger apoptosis in HL-60 cells.

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Funding

This study was funded by the National Natural Science Foundation of China (No. 81500135).

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Authors and Affiliations

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

    Liang Peiqi, Hu Rong, Liu Zhuogang, Jiang Wei & Miao Miao

  2. Anatomy Department, China Medical University, Shenyang, China

    Dong Hongming

Authors
  1. Liang Peiqi
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  2. Hu Rong
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  3. Dong Hongming
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  4. Liu Zhuogang
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  5. Jiang Wei
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  6. Miao Miao
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Correspondence to Hu Rong.

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The authors declare that there is no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Peiqi, L., Rong, H., Hongming, D. et al. GDC-0152-induced autophagy promotes apoptosis in HL-60 cells. Mol Cell Biochem 445, 135–143 (2018). https://doi.org/10.1007/s11010-017-3259-7

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  • DOI: https://doi.org/10.1007/s11010-017-3259-7

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