benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and dioscin

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.

Topics: Amino Acid Chloromethyl Ketones; Apoptosis; Carcinoma, Renal Cell; CASP8 and FADD-Like Apoptosis Regulating Protein; Caspase 3; Diosgenin; Down-Regulation; Humans; Kidney Neoplasms; Myeloid Cell Leukemia Sequence 1 Protein; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; RNA, Messenger; TNF-Related Apoptosis-Inducing Ligand