Inhibition of expression of anti-apoptotic protein Bcl-2 and induction of cell death in radioresistant human prostate adenocarcinoma cell line (PC-3) by methyl jasmonate

Cancer Lett. 2008 Nov 8;270(2):277-85. doi: 10.1016/j.canlet.2008.05.022. Epub 2008 Jun 24.

Abstract

Hormone refractory human prostate cancer cell lines are known to be radioresistant, a feature attributed to their ability to induce anti-apoptotic proteins of the Bcl-2 family when exposed to radiation. We investigated whether pro-apoptotic compounds such as methyl jasmonate, a plant stress hormone, can counteract the radiation-induced anti-apoptotic mechanism in a human prostate cancer cell line PC-3. Significant (p<0.05) increase in cytotoxicity was observed in the combined treatment groups compared to single treatments with methyl jasmonate or gamma-radiation. Treatment of irradiated PC-3 cells with methyl jasmonate resulted in suppression of anti-apoptotic Bcl-2 protein and elevation of caspase-3 activity. Our results showed increased apoptosis in the combined treatment group as compared to the irradiated group or the untreated control. In summary, methyl jasmonate suppressed the radiation-induced Bcl-2 expression and enhanced the radiation sensitivity of human prostate cancer cells.

MeSH terms

  • Acetates / pharmacology*
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Annexin A5 / metabolism
  • Apoptosis* / drug effects
  • Apoptosis* / radiation effects
  • Caspase 3 / metabolism
  • Cell Death
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Cyclopentanes / pharmacology*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Gamma Rays*
  • Humans
  • Male
  • Oxylipins / pharmacology*
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Radiation Tolerance*
  • Radiation-Sensitizing Agents / pharmacology*

Substances

  • Acetates
  • Annexin A5
  • Cyclopentanes
  • Oxylipins
  • Proto-Oncogene Proteins c-bcl-2
  • Radiation-Sensitizing Agents
  • methyl jasmonate
  • CASP3 protein, human
  • Caspase 3