APG-1252-12A induces mitochondria-dependent apoptosis through inhibiting the antiapoptotic proteins Bcl-2/Bcl-xl in HL-60 cells

  • Authors:
    • Jing Wang
    • Dajun Yang
    • Qiuyun Luo
    • Miaozhen Qiu
    • Lin Zhang
    • Baoxia Li
    • Haibo Chen
    • Hanjie Yi
    • Xianglei Yan
    • Shuxia Li
    • Jian Sun
  • View Affiliations

  • Published online on: June 6, 2017     https://doi.org/10.3892/ijo.2017.4028
  • Pages: 563-572
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Abstract

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Despite improved remission rates, current treatment regimens for AML are often associated with a very poor prognosis and adverse effects, necessitating more effective and safer agents. B-cell leukemia/lymphoma 2 (Bcl-2) family proteins regulate apoptotic pathway that can be targeted with small molecule inhibitors. APG-1252-12A is a Bcl-2 homology (BH)-3 mimetic that specifically binds to Bcl-2 and Bcl-xl, which has shown efficacy in some Bcl-2 dependent hematological cancers. In this study, we investigated whether APG-1252-12A inhibits the growth of five leukemia cell lines in a concentration- or time-dependent manner by MTS assay. Following treatment of AML cell line HL-60 with this compound, cell apoptosis was detected using flow cytometry and nuclear condensation was observed after Hoechst 33258 dye. Immunoblotting for cytochrome c, cleaved caspase-3 and PARP-1 cleavage was used to demonstrate the mechanism of inducing mitochondria-dependent apoptosis by APG-1252-12A. Our findings showed that this new compound inhibited cell proliferation in five leukemia cell lines and induced apoptotic death. There was a link between the level of Bcl-2 protein and IC50. APG-1252-12A targeted mitochondria and induced caspase-dependent apoptosis by inducing the HL-60 cell cytochrome c released, PARP cleavage and caspase activation. These data suggested that APG-1252-12A is a candidate drug for the in vivo analysis and clinical evaluation in AML.
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August-2017
Volume 51 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Wang J, Yang D, Luo Q, Qiu M, Zhang L, Li B, Chen H, Yi H, Yan X, Li S, Li S, et al: APG-1252-12A induces mitochondria-dependent apoptosis through inhibiting the antiapoptotic proteins Bcl-2/Bcl-xl in HL-60 cells. Int J Oncol 51: 563-572, 2017.
APA
Wang, J., Yang, D., Luo, Q., Qiu, M., Zhang, L., Li, B. ... Sun, J. (2017). APG-1252-12A induces mitochondria-dependent apoptosis through inhibiting the antiapoptotic proteins Bcl-2/Bcl-xl in HL-60 cells. International Journal of Oncology, 51, 563-572. https://doi.org/10.3892/ijo.2017.4028
MLA
Wang, J., Yang, D., Luo, Q., Qiu, M., Zhang, L., Li, B., Chen, H., Yi, H., Yan, X., Li, S., Sun, J."APG-1252-12A induces mitochondria-dependent apoptosis through inhibiting the antiapoptotic proteins Bcl-2/Bcl-xl in HL-60 cells". International Journal of Oncology 51.2 (2017): 563-572.
Chicago
Wang, J., Yang, D., Luo, Q., Qiu, M., Zhang, L., Li, B., Chen, H., Yi, H., Yan, X., Li, S., Sun, J."APG-1252-12A induces mitochondria-dependent apoptosis through inhibiting the antiapoptotic proteins Bcl-2/Bcl-xl in HL-60 cells". International Journal of Oncology 51, no. 2 (2017): 563-572. https://doi.org/10.3892/ijo.2017.4028