Diosgenin induces death receptor-5 through activation of p38 pathway and promotes TRAIL-induced apoptosis in colon cancer cells

Cancer Lett. 2011 Feb 28;301(2):193-202. doi: 10.1016/j.canlet.2010.12.003. Epub 2010 Dec 30.

Abstract

Previously, we demonstrated that diosgenin induced apoptosis in colorectal cancer cell lines HCT-116 and HT-29. HT-29 cells have been reported to be one of the most resistant colorectal cancer cell lines to TRAIL-induced apoptosis. In this study, we investigated the effect of diosgenin on TRAIL-induced apoptosis in HT-29 cells. We showed that diosgenin sensitizes HT-29 cells to TRAIL-induced apoptosis. Mechanisms underlying this sensitization mainly involved diosgenin-induced p38 MAPK pathway activation and subsequent DR5 overexpression. Furthermore, we showed that diosgenin alone, TRAIL alone or combination treatment increased COX-2 expression and that the use of a COX-2 inhibitor further increased apoptosis induction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Cyclooxygenase 2 / metabolism
  • Diosgenin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Enzyme Inhibitors / pharmacology
  • HT29 Cells
  • Humans
  • Imidazoles / pharmacology
  • MAP Kinase Signaling System / drug effects
  • Microscopy, Phase-Contrast
  • Pyridines / pharmacology
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism*
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*
  • Up-Regulation / drug effects
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Enzyme Inhibitors
  • Imidazoles
  • Pyridines
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • TNF-Related Apoptosis-Inducing Ligand
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • p38 Mitogen-Activated Protein Kinases
  • Diosgenin
  • SB 203580