Casticin, a flavonoid, potentiates TRAIL-induced apoptosis through modulation of anti-apoptotic proteins and death receptor 5 in colon cancer cells

Oncol Rep. 2013 Feb;29(2):474-80. doi: 10.3892/or.2012.2127. Epub 2012 Nov 7.

Abstract

We investigated the effect of casticin on apoptosis induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). We found that casticin potentiated TRAIL-induced apoptosis in human colon cancer cells. Casticin downregulated cell survival proteins including Bcl-xL, Bcl-2, survivin, XIAP and cFLIP, and induced death receptor 5 (DR5), but had no effect on DR4 and decoy receptors (DcR1 or DcR2). Deletion of DR5 by siRNA significantly reduced the apoptosis induced by TRAIL and casticin. In addition, casticin induced reactive oxygen species (ROS) generation in a dose-dependent manner. Collectively, the present study showed that casticin potentiates TRAIL-induced apoptosis through downregulation of cell survival proteins and induction of DR5 mediated by ROS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism*
  • Colonic Neoplasms / metabolism*
  • Down-Regulation / drug effects
  • Flavonoids / pharmacology*
  • GPI-Linked Proteins / metabolism
  • Gene Silencing
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / biosynthesis*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Receptors, Tumor Necrosis Factor, Member 10c
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*
  • Tumor Necrosis Factor Decoy Receptors / metabolism
  • Up-Regulation / drug effects
  • X-Linked Inhibitor of Apoptosis Protein / metabolism
  • bcl-X Protein / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • BCL2L1 protein, human
  • BIRC5 protein, human
  • Flavonoids
  • GPI-Linked Proteins
  • Inhibitor of Apoptosis Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor, Member 10c
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10C protein, human
  • TNFRSF10D protein, human
  • TNFSF10 protein, human
  • Tumor Necrosis Factor Decoy Receptors
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • bcl-X Protein
  • casticin