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.
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.
Ezekwudo
Daniel
D
Department of Pathology and Laboratory Medicine, Woodruff Memorial Research Building, 101 Woodruff Circle, WMB Rm 7309, Emory University School of Medicine, Atlanta, GA 30322, USA.
Shashidharamurthy
Rangaiah
R
Devineni
Dilip
D
Bozeman
Erica
E
Palaniappan
Ravi
R
Selvaraj
Periasamy
P
D000085:Acetates / Q000494:pharmacology*; D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003517:Cyclopentanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005720:Gamma Rays; D006801:Humans; D008297:Male; D054883:Oxylipins / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D000085:Acetates; D017304:Annexin A5; D003517:Cyclopentanes; D054883:Oxylipins; D019253:Proto-Oncogene Proteins c-bcl-2; D011838:Radiation-Sensitizing Agents; C072239:methyl jasmonate; C505407:CASP3 protein, human; D053148:Caspase 3