Activation of peroxisome proliferator-activated receptor-γ induces apoptosis on acute promyelocytic leukemia cells via downregulation of XIAP

  • Authors:
    • Jia-Jun Liu
    • Yun-Wei Guo
    • Zhi-Gang Fang
    • Xiao-Ning Si
    • Xiang-Yuan Wu
    • Pei-Qing Liu
    • Dong-Jun Lin
    • Ruo-Zhi Xiao
    • Yan Xu
    • Chun-Zhi Wang
    • Xu-Dong Li
    • Yi He
    • Ren-Wei Huang
  • View Affiliations

  • Published online on: November 1, 2009     https://doi.org/10.3892/ijmm_00000273
  • Pages: 623-632
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Abstract

In the present study we investigated the in vitro apoptosis inducing effects of peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand ciglitazone (CGZ) on acute promyelocytic leukemia (APL) NB4 cells and its mechanisms of action. The results revealed that CGZ (10-50 µmol/l) inhibited the growth of leukemia NB4 cells and caused apoptosis in a time- and dose-dependent manner. Apoptosis was observed clearly by flow cytometry (FCM) and DNA fragmentation analysis. After treatment by CGZ for 48 h, the percentage of disruption of mitochondrial membrane potential (Δψm) was increased in a dose-dependent manner. Western blotting demonstrated the cleavage of caspase-3 zymogen protein and a time-dependent cleavage of poly (ADP-ribose) polymerase (PARP). The results also demonstrated that PPAR-γ expression was increased concomitantly when apoptosis occurred, and that CGZ-induced apoptosis was inhibited by the PPAR-γ antagonist GW9662, suggesting a PPAR-γ dependent signaling pathway in CZG-induced cell death. Moreover, CGZ treatment remarkably downregulated the expression of the X-linked inhibitor of apoptosis protein (XIAP), which was inhibited by GW9662. Of note, a small-molecule XIAP antagonist (1396-12) mimicked the effect of CGZ-induced apoptosis via activation of caspase-3, 7 and 9. The apoptosis-inducing effects by CGZ on fresh APL cells were also found to be remarkable by using FCM and Wright's staining observation. Taken together, our results suggest that downregulation of XIAP and activation of capase-3 play an important role in mediating the PPAR-γ-dependent cell death induced by CGZ in APL cells. These data provide a novel insight into potential therapeutic strategies for treatment of leukemia.

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November 2009
Volume 24 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Liu J, Guo Y, Fang Z, Si X, Wu X, Liu P, Lin D, Xiao R, Xu Y, Wang C, Wang C, et al: Activation of peroxisome proliferator-activated receptor-γ induces apoptosis on acute promyelocytic leukemia cells via downregulation of XIAP. Int J Mol Med 24: 623-632, 2009
APA
Liu, J., Guo, Y., Fang, Z., Si, X., Wu, X., Liu, P. ... Huang, R. (2009). Activation of peroxisome proliferator-activated receptor-γ induces apoptosis on acute promyelocytic leukemia cells via downregulation of XIAP. International Journal of Molecular Medicine, 24, 623-632. https://doi.org/10.3892/ijmm_00000273
MLA
Liu, J., Guo, Y., Fang, Z., Si, X., Wu, X., Liu, P., Lin, D., Xiao, R., Xu, Y., Wang, C., Li, X., He, Y., Huang, R."Activation of peroxisome proliferator-activated receptor-γ induces apoptosis on acute promyelocytic leukemia cells via downregulation of XIAP". International Journal of Molecular Medicine 24.5 (2009): 623-632.
Chicago
Liu, J., Guo, Y., Fang, Z., Si, X., Wu, X., Liu, P., Lin, D., Xiao, R., Xu, Y., Wang, C., Li, X., He, Y., Huang, R."Activation of peroxisome proliferator-activated receptor-γ induces apoptosis on acute promyelocytic leukemia cells via downregulation of XIAP". International Journal of Molecular Medicine 24, no. 5 (2009): 623-632. https://doi.org/10.3892/ijmm_00000273