Combination treatment of hydrogen peroxide and X-rays induces apoptosis in human prostate cancer PC-3 cells.
OBJECTIVE
To study the effect of hydrogen peroxide (H(2)O(2)) on radiation-induced apoptosis in human prostate cancer PC-3 cells.


METHODS
At 4h before the irradiation, PC-3 cells were exposed to 10mM ammonium chloride (NH(4)Cl) concentrations. Subsequently, cells were exposed to 0.1mM H(2)O(2) just before the irradiations, which were administered with 10-MV X-rays at doses of 10 Gy.


RESULTS
The percentage of apoptotic cells at 48 h after X-irradiation alone, H(2)O(2) alone, and combined X-irradiation and H(2)O(2) was 1.85%, 4.85%, and 28.4%, respectively. With use of combined X-irradiation and H(2)O(2), production of reactive oxygen species (ROS) occurred 4h after the irradiation. This resulted in lysosomal rupturing, mitochondrial fragmentation, and the release of cytochrome c into the cytoplasm from the mitochondria. In contrast, when cells were exposed to NH(4)Cl before the X-irradiation and H(2)O(2) administration, apoptosis was almost completely suppressed, ROS production did not occur, lysosomal rupture and mitochondrial fragmentation were blocked, and cytochrome c was not released.


CONCLUSIONS
Hydrogen peroxide strongly enhanced lysosome-dependent radiation-induced apoptosis in human prostate cancer PC-3 cells. A combined use of X-rays and H(2)O(2) can also injure the mitochondrial cytoplasmic organelles and lead to the production of ROS that in and of itself might possibly induce apoptosis.
Kariya
Shinji
S
Department of Diagnostic Radiology and Radiation Oncology, Kochi Medical School, Kochi, Japan. kariyas@kochi-u.ac.jp
Sawada
Ken
K
Kobayashi
Toshihiro
T
Karashima
Takashi
T
Shuin
Taro
T
Nishioka
Akihito
A
Ogawa
Yasuhiro
Y
D000643:Ammonium Chloride / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000528:radiation effects; D015388:Organelles / Q000187:drug effects / Q000528:radiation effects; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011879:Radiotherapy Dosage; D017382:Reactive Oxygen Species / Q000378:metabolism
D016877:Oxidants; D017382:Reactive Oxygen Species; D000643:Ammonium Chloride; D045304:Cytochromes c; D006861:Hydrogen Peroxide