Resveratrol promotes differentiation and induces Fas-independent apoptosis of human medulloblastoma cells

Neurosci Lett. 2003 Nov 13;351(2):83-6. doi: 10.1016/j.neulet.2003.07.002.

Abstract

Resveratrol has tumor-suppressive activities in some in vitro and in vivo experimental systems but its effect on medulloblastoma cells is still unknown. In this study, resveratrol was used to treat four human medulloblastoma cell lines (Med-3, UW228-1, -2 and -3) and its effects on cell growth, differentiation and death were examined by multiple approaches. Expression of Fas, FasL and caspase-3 in the cells without and with resveratrol treatments was examined by immunocytochemical staining and mRNA in situ hybridization and the influence of anti-Fas antibody (200 ng/ml) in cell growth and survival was determined as well. The results demonstrated that resveratrol could suppress growth, promote differentiation and commit its target cells to apoptosis in time- and dose-related fashions. Fas was constitutively expressed but FasL was undetectable in the four lines in spite of resveratrol treatment. Anti-Fas antibody (200 ng/ml) neither inhibited growth nor induced apoptosis of those cell lines. Up-regulated caspase-3 was found in resveratrol-treated populations and appearance of its cleaved form was closely associated with the apoptotic event. These findings suggest for the first time that resveratrol is an effective anti-medulloblastoma agent that kills medulloblastoma cells through a Fas-independent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis* / drug effects
  • Apoptosis* / physiology
  • Caspase 3
  • Caspases / genetics
  • Caspases / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cerebellar Neoplasms / drug therapy*
  • Cerebellar Neoplasms / metabolism
  • Cerebellar Neoplasms / physiopathology
  • Dose-Response Relationship, Drug
  • Fas Ligand Protein
  • Humans
  • Medulloblastoma / drug therapy*
  • Medulloblastoma / metabolism
  • Medulloblastoma / physiopathology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • RNA, Messenger / metabolism
  • Resveratrol
  • Stilbenes / pharmacology*
  • Stilbenes / therapeutic use
  • Up-Regulation / drug effects
  • Up-Regulation / physiology
  • fas Receptor / drug effects
  • fas Receptor / genetics
  • fas Receptor / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • RNA, Messenger
  • Stilbenes
  • fas Receptor
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Resveratrol