Increased expression of peroxiredoxin II confers resistance to cisplatin.
Peroxiredoxin II (Prx II) has been known to be induced by various oxidative stimuli and to play an important protective role from oxidative damage by hydrogen peroxide (H2O2). In this study, we observed that cisplatin as well as H2O2 induced Prx II expression. To examine the correlation between the increased expression of Prx II and chemoresistance, we prepared a Prx II-overexpressing cell line, SNU638 cells, and found it to be more resistant to cell death induced by cisplatin and H2O2 than neo-transfectant cells. We also observed that enhanced expression of Prx II inhibited cisplatin- and H2O2-induced apoptosis, demonstrating that resistance to these cytotoxic agents was due to inhibition of apoptosis. The above results led us to suggest that the overexpressed Prx II protein inhibits cisplatin-induced apoptosis, thereby contributing to chemoresistance of tumor cells, especially to oxidative stress producing anticancer drugs.
Chung
Y M
YM
Laboratory of Experimental Therapeutics, Korea Cancer Center Hospital, Seoul 139-706, Korea.
Yoo
Y D
YD
Park
J K
JK
Kim
Y T
YT
Kim
H J
HJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D010544:Peroxidases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D054464:Peroxiredoxins; D013274:Stomach Neoplasms / Q000188:drug therapy; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000975:Antioxidants; D006861:Hydrogen Peroxide; D010544:Peroxidases; D054464:Peroxiredoxins; D002945:Cisplatin