3,3',4,5,5'-Pentahydroxy-trans-stilbene, a resveratrol derivative, induces apoptosis in colorectal carcinoma cells via oxidative stress

Eur J Pharmacol. 2010 Jul 10;637(1-3):55-61. doi: 10.1016/j.ejphar.2010.04.009. Epub 2010 Apr 23.

Abstract

Resveratrol exhibits anti-tumor properties against different types of cancer. In this study, several polyhydroxylated resveratrol derivatives were prepared with the aim of discovering new leading compounds with clinical potential for human colon cancer chemotherapy. Among these compounds, 3,3',4,5,5'-pentahydroxy-trans-stilbene (PHS) displayed the most potent cytotoxicity and triggered apoptosis in HT-29 cells as evidenced by increased poly(ADP-ribose) polymerase (PARP) cleavage, elevated levels of cytoplasmic nucleosomes and DNA fragmentation. Further mechanistic analysis revealed that PHS-induced apoptosis was caspase-dependent and mediated by its pro-oxidative action through up-regulation of reactive oxidative species generation and depletion of intracellular glutathione.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Cytoplasm / metabolism
  • DNA Fragmentation / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Glutathione / metabolism
  • HT29 Cells
  • Humans
  • Nucleosomes / metabolism
  • Oxidative Stress / drug effects*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Resveratrol
  • Stilbenes / chemistry*
  • Stilbenes / pharmacology*
  • Tumor Cells, Cultured
  • Up-Regulation / drug effects

Substances

  • 3,5,3',4',5'-pentahydroxy-stilbene
  • Antineoplastic Agents
  • Nucleosomes
  • Stilbenes
  • Poly(ADP-ribose) Polymerases
  • Glutathione
  • Resveratrol