Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has received attention as a potential anticancer drug, because it induces apoptosis in a wide variety of cancer cells but not in most normal human cell types. Here, we showed that co-treatment with subtoxic doses of dioscin and TRAIL-induced apoptosis in Caki human renal cancer cells. Treatment of Caki cells with dioscin downregulated c-FLIPL and Bcl-2 proteins in a dose-dependent manner. Dioscin-induced decrease in c-FLIPL protein levels may be caused by the increased protein instability. We also found that dioscin induced downregulation of Bcl-2 at the transcriptional level. Pretreatment with NAC slightly inhibited the expression levels of c-FLIPL downregulated by the treatment of dioscin, suggesting that dioscin is partially dependent on the generation of ROS for downregulation of c-FLIPL. Taken together, the present study demonstrates that dioscin enhances TRAIL-induced apoptosis in human renal cancer cells by downregulation of c-FLIPL and Bcl-2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Chloromethyl Ketones / pharmacology
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Apoptosis / drug effects*
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CASP8 and FADD-Like Apoptosis Regulating Protein / genetics
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CASP8 and FADD-Like Apoptosis Regulating Protein / metabolism*
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Carcinoma, Renal Cell / drug therapy
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Carcinoma, Renal Cell / metabolism
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Caspase 3 / metabolism
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Diosgenin / analogs & derivatives*
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Diosgenin / pharmacology
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Down-Regulation
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Humans
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Kidney Neoplasms / drug therapy
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Kidney Neoplasms / metabolism
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Myeloid Cell Leukemia Sequence 1 Protein
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Poly(ADP-ribose) Polymerases / metabolism
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reactive Oxygen Species / metabolism
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TNF-Related Apoptosis-Inducing Ligand / metabolism
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TNF-Related Apoptosis-Inducing Ligand / pharmacology*
Substances
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Amino Acid Chloromethyl Ketones
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CASP8 and FADD-Like Apoptosis Regulating Protein
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CFLAR protein, human
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Myeloid Cell Leukemia Sequence 1 Protein
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Reactive Oxygen Species
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
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dioscin
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Poly(ADP-ribose) Polymerases
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Caspase 3
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Diosgenin