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 therap y. Hormone-independent prostate cancer usually exhibits resistance to chemo therapy and radiotherapy. Antioxidant systems are known to be involved in t he 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 dismuta se, catalase, and glutathione peroxidase, and for levels of protein and non protein thiols such as metallothionein, glutathione, and thioredoxin. Sensi tivity of these cells to anticancer drugs and inducers of reactive oxygen s pecies 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 r esistant 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 hig her levels of glutathione and metallothionein than HPC36M. CONCLUSIONS. These data suggest that enhanced ability in scavenging free ra dicals by antioxidant enzymes and thiol compounds may, at least in part, co ntribute to the resistance of bone metastatic prostate cancer during chemot herapy. (C) 2000 Wiley-Liss, Inc.