Resveratrol and clofarabine induces a preferential apoptosis-activating effect on malignant mesothelioma cells by Mcl-1 down-regulation and caspase-3 activation |
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Authors: | Yoon-Jin Lee Yong-Jin Lee Sang-Han Lee |
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Institution: | 1.Soonchunhyung Environmental Health Center for Asbestos, Korea;2.Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Korea;3.Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 330-090, Korea |
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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 down-regulation 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. BMB Reports 2015; 48(3): 166-171] |
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Keywords: | Chemosensitivity Clofarabine MeT-5A MSTO-211H Resveratrol |
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