Dioscin sensitizes cells to TRAIL-induced apoptosis through downregulation of c-FLIP and Bcl-2

Oncol Rep. 2012 Nov;28(5):1910-6. doi: 10.3892/or.2012.1962. Epub 2012 Aug 9.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Apoptosis / drug effects*
  • CASP8 and FADD-Like Apoptosis Regulating Protein / genetics
  • CASP8 and FADD-Like Apoptosis Regulating Protein / metabolism*
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / metabolism
  • Caspase 3 / metabolism
  • Diosgenin / analogs & derivatives*
  • Diosgenin / pharmacology
  • Down-Regulation
  • Humans
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / metabolism
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • TNF-Related Apoptosis-Inducing Ligand / metabolism
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*

Substances

  • Amino Acid Chloromethyl Ketones
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Reactive Oxygen Species
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • dioscin
  • Poly(ADP-ribose) Polymerases
  • Caspase 3
  • Diosgenin