title: Resveratrol and clofarabine induces a preferential apoptosis-activating effect on malignant mesothelioma cells by Mcl-1 down-regulation and caspase-3 activation.
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.
authors.affiliation: Soonchunhyung Environmental Health Center for Asbestos; Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Cheonan 330-090, Korea.
authors.forename: Yoon-Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Soonchunhyung Environmental Health Center for Asbestos, College of Medicine, Soonchunhyang University, Cheonan 330-090, Korea.
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Soonchunhyung Environmental Health Center for Asbestos; Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 330-090, Korea.
authors.forename: Sang-Han
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000227:Adenine Nucleotides / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001087:Arabinonucleosides / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D000077866:Clofarabine; D015536:Down-Regulation / Q000187:drug effects*; D004789:Enzyme Activation; D006801:Humans; D008654:Mesothelioma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D013267:Stilbenes; D000077866:Clofarabine; D053148:Caspase 3; D000077185:Resveratrol