Dioscin sensitizes cells to TRAIL-induced apoptosis through downregulation             of c-FLIP and Bcl-2.
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.
Department of Microbiology and Immunology, School of Medicine,                     Soonchunhyang University, Cheonan, Chungnam 330-090, Republic of Korea.
Yong-Sik
YS
Kim
Eun-Ae
EA
Kim
Kyu-Gun
KG
Park
Sung-Jun
SJ
Lee
Mi-Sun
MS
Kim
Ho-Yong
HY
Sohn
Tae-Jin
TJ
Lee
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism / Q000494:pharmacology*
D000590:Amino Acid Chloromethyl Ketones; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C019357:dioscin; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D004144:Diosgenin