methyl-jasmonate and Adenocarcinoma

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.

Topics: Acetates; Adenocarcinoma; Annexin A5; Apoptosis; Caspase 3; Cell Death; Cell Line, Tumor; Cell Proliferation; Cyclopentanes; Dose-Response Relationship, Drug; Down-Regulation; Gamma Rays; Humans; Male; Oxylipins; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Radiation Tolerance; Radiation-Sensitizing Agents

Jasmonates are plant lipid derivatives, similar to mammalian eicosanoid, that play a critical role(s) in plant defenses against herbivores and pathogens through up-regulating the expression of defense-related genes. Recently, jasmonates were shown to induce cell cycle arrest or apoptosis in human leukemia, prostate and breast cancer cells, but not in normal lymphocytes, suggesting that the chemicals can be used as a novel class of anti-cancer drugs. In the present study, we examined the molecular mechanism that contributes to methyl jasmonate-induced apoptosis. Herein we show that methyl jasmonate induces apoptosis through induction of Bax/Bcl-XS and activation of caspase-3 via reactive oxygen species production in A549 human lung adenocarcinoma cells.

Topics: Acetates; Adenocarcinoma; Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Blotting, Western; Caspase 3; Caspases; Cell Line, Tumor; Cyclopentanes; Electrophoresis, Polyacrylamide Gel; Enzyme Activation; Humans; Membrane Potentials; Microscopy, Confocal; Mitochondria; Oxylipins; Plant Growth Regulators; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species