Combined action of celecoxib and ionizing radiation in prostate cancer cells is independent of pro-apoptotic Bax.
OBJECTIVE
The cyclooxygenase-2-inhibitor celecoxib has been shown to inhibit cell growth and to reduce prostatic intraepithelial neoplasia in mice. The drug was suggested to increase efficacy of ionizing radiation. However, extent and mechanisms of the suggested benefit of celecoxib on the radiation response are still unclear. The aim of the present study was to analyze cytotoxic efficacy of celecoxib in combination with irradiation on human prostate cancer cell lines and to define the importance of pro-apoptotic Bax in this process.


METHODS
Induction of apoptosis and global and clonogenic cell survival upon irradation- (2-10Gy), celecoxib- (10-75microM) or combined treatment were evaluated in prostate cancer cells by fluorescence microscopy, WST-1 assay and standard colony formation assays.


RESULTS
Celecoxib <25microM caused morphological changes and growth inhibition without substantial apoptosis or radiosensitization in terms of decreased clonogenic cell survival. In contrast, celecoxib 25microM increased radiation-induced cell death and clonogenic kill. While radiation-induced clonogenic death was increased in the presence of Bax, effects of celecoxib or combined treatment were Bax independent.


CONCLUSIONS
Our findings reveal Bax-independent beneficial effects of celecoxib on radiation-induced apoptosis and eradication of clonogenic prostate cancer cells in vitro providing a rationale for clinical evaluation of high-dose celecoxib in combination with irradiation in prostate cancer patients.
Handrick
René
R
Department of Radiation Oncology, University of Tübingen, Germany.
Ganswindt
Ute
U
Faltin
Heidrun
H
Goecke
Barbara
B
Daniel
Peter T
PT
Budach
Wilfried
W
Belka
Claus
C
Jendrossek
Verena
V
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects*; D000068579:Celecoxib; D045744:Cell Line, Tumor; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib