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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Resveratrol and clofarabine induces a preferential apoptosis-activating effect on malignant mesothelioma cells by Mcl-1 down-regulation and caspase-3 activation

  • Lee, Yoon-Jin (Soonchunhyung Environmental Health Center for Asbestos, College of Medicine, Soonchunhyang University) ;
  • Lee, Yong-Jin (Soonchunhyung Environmental Health Center for Asbestos, College of Medicine, Soonchunhyang University) ;
  • Lee, Sang-Han (Soonchunhyung Environmental Health Center for Asbestos, College of Medicine, Soonchunhyang University)
  • Received : 2014.05.15
  • Accepted : 2014.06.13
  • Published : 2015.03.31
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Abstract

We previously demonstrated that resveratrol and clofarabine elicited a marked cytotoxicity on malignant mesothelioma (MM) MSTO-211H cells but not on the corresponding normal mesothelial MeT-5A cells. Little is known of the possible molecules that could be used to predict preferential chemosensitivity on MSTO-211H cells. Resveratrol and clofarabine induced downregulation of Mcl-1 protein level in MSTO-211H cells. Treatment of cells with cycloheximide in the presence of proteasome inhibitor MG132 suggested that Mcl-1 protein levels were regulated at the post-translational step. The siRNA-based knockdown of Mcl-1 in MSTO-211H cells triggered more growth-inhibiting and apoptosis-inducing effects with the resultant cleavages of procaspase-3 and its substrate PARP, increased caspase-3/7 activity, and increased percentage of apoptotic propensities. However, the majority of the observed changes were not shown in MeT-5A cells. Collectively, these studies indicate that the preferential activation of caspase cascade in malignant cells might have important applications as a therapeutic target for MM.

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References

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