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Autophagy inhibition enhances isobavachalcone-induced cell death in multiple myeloma cells

  • Authors:
    • Shan Zhao
    • Chun-Min Ma
    • Chuan-Xu Liu
    • Wei Wei
    • Yun Sun
    • Hua Yan
    • Ying-Li Wu

  • View Affiliations

  • Published online on: July 16, 2012     https://doi.org/10.3892/ijmm.2012.1066
  • Pages: 939-944
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
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Abstract

Despite recent advancements in therapeutic drugs, multiple myeloma remains an incurable disease. Therefore, a more effective treatment is urgently required. In this study, we show that isobavachalcone (IBC), a natural chalcone compound, induces apoptosis- and autophagy-related cell death in myeloma cells. The inhibition of autophagy by knocking down beclin-1 or by using autophagy inhibitors, such as 3-methyladenine, bafilomycin A and chloroquine significantly enhanced IBC-induced cell death, as demonstrated by the increased number of Annexin V-positive cells. Moreover, we demonstrate that the collapse of the mitochondrial membrane potential contributes to chloroquine and IBC-induced cell death, which is accompanied by the activation of caspase-9, and -3, the cleavage of poly (ADP-ribose) polymerase (PARP) and the proteolytic activation of protein kinase Cδ (PKCδ). Furthermore, the inhibition of the activation of PKCδ by rottlerin, an inhibitor of PKCδ, not only suppressed the activation of PKCδ, but also the apoptosis induced by the co-treatment of chloroquine and IBC, indicating the involvement of PKCδ in chloroquine plus IBC-induced cell death. Finally, the combination of chloroquine and IBC had little effect on the viability of normal peripheral blood mononuclear cells. As both chloroquine and IBC have been shown to be relatively specific for cancer cells, the combination of these two agents at non-toxic or sub-toxic concentrations represents an attractive novel regimen for myeloma treatment and warrants further investigation in preclinical and clinical studies.
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Journal Cover

October 2012
Volume 30 Issue 4

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

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  • Journal Metrics
  • Impact Factor: 5.4
  • Ranked Medicine Research and Experimental
    (total number of cites)
  • CiteScore: 10.7
  • CiteScore Rank: Q1: #35/328 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 0.994
  • SCImago Journal Rank (SJR): 0.922
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Spandidos Publications style
Zhao S, Ma C, Liu C, Wei W, Sun Y, Yan H and Wu Y: Autophagy inhibition enhances isobavachalcone-induced cell death in multiple myeloma cells. Int J Mol Med 30: 939-944, 2012
APA
Zhao, S., Ma, C., Liu, C., Wei, W., Sun, Y., Yan, H., & Wu, Y. (2012). Autophagy inhibition enhances isobavachalcone-induced cell death in multiple myeloma cells. International Journal of Molecular Medicine, 30, 939-944. https://doi.org/10.3892/ijmm.2012.1066
MLA
Zhao, S., Ma, C., Liu, C., Wei, W., Sun, Y., Yan, H., Wu, Y."Autophagy inhibition enhances isobavachalcone-induced cell death in multiple myeloma cells". International Journal of Molecular Medicine 30.4 (2012): 939-944.
Chicago
Zhao, S., Ma, C., Liu, C., Wei, W., Sun, Y., Yan, H., Wu, Y."Autophagy inhibition enhances isobavachalcone-induced cell death in multiple myeloma cells". International Journal of Molecular Medicine 30, no. 4 (2012): 939-944. https://doi.org/10.3892/ijmm.2012.1066