Role of antioxidant systems in human androgen-independent prostate cancer cells.
BACKGROUND
Most prostate cancer cells respond to initial hormonal therapy; however, some of them eventually acquire resistance to the hormonal therapy. Hormone-independent prostate cancer usually exhibits resistance to chemotherapy and radiotherapy. Antioxidant systems are known to be involved in the resistance of cancer cells to chemotherapy and radiotherapy. Therefore, it is of significance to examine antioxidant systems of hormone-independent prostate cancer for enhancing the efficacy of cancer therapy.


METHODS
Three cell lines of human hormone-independent prostate cancer (PC-3, PC-3 MA2, and HPC36M) were examined for activities of superoxide dismutase, catalase, and glutathione peroxidase, and for levels of protein and nonprotein thiols such as metallothionein, glutathione, and thioredoxin. Sensitivity of these cells to anticancer drugs and inducers of reactive oxygen species such as paraquat, tert-butylhydroperoxide, and hydrogen peroxide was determined by microtiter assay.


RESULTS
PC-3 and PC-3 MA2, which were derived from bone metastases, were resistant to paraquat, hydrogen peroxide, and cisplatin compared with HPC36M, which was obtained from the primary prostate cancer. However, HPC36M was resistant to vinblastine compared with PC-3 and PC-3 MA2. Both PC-3 and PC-3 MA2 had higher activities of catalase and glutathione peroxidase and higher levels of glutathione and metallothionein than HPC36M.


CONCLUSIONS
These data suggest that enhanced ability in scavenging free radicals by antioxidant enzymes and thiol compounds may, at least in part, contribute to the resistance of bone metastatic prostate cancer during chemotherapy.
Suzuki
Y
Y
Department of Urology, Nippon Medical School, Tokyo, Japan.
Kondo
Y
Y
Himeno
S
S
Nemoto
K
K
Akimoto
M
M
Imura
N
N
D000728:Androgens / Q000502:physiology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D006801:Humans; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000728:Androgens; D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D010088:Oxidoreductases