Overexpressed cyclophilin A in cancer cells renders resistance to hypoxia- and cisplatin-induced cell death.
Cyclophilin A (CypA) has been reported to be overexpressed in cancer cells, especially in solid tumors. To determine the role of CypA in tumorigenesis, we investigated the induction of CypA as well as the role it plays in cancer cells. Here, we have shown that induction of CypA is associated with hypoxia in a variety of cells, including DU145 human prostate cancer cell line. Our analysis of the CypA promoter clearly showed that CypA up-regulation is mediated by hypoxia-inducible factor-1alpha transcription factor. Interestingly, overexpression of CypA prevented hypoxia- and cisplatin-induced apoptosis, and this was associated with the suppression of reactive oxygen species generation and depolarization of mitochondrial membrane potential, whereas small interfering RNA-based CypA knockdown aggravated these factors. These results suggest that CypA is important in tumorigenesis, especially in tumor apoptosis.
Choi
Kyu Jin
KJ
Department of Biochemistry and Molecular Biology, Medical Science and Engineering Research Center for Bioreaction to Reactive Oxygen Species, School of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemoon-gu, Seoul 130-701, Korea.
Piao
Yu Ji
YJ
Lim
Min Jin
MJ
Kim
Jin Hwan
JH
Ha
Joohun
J
Choe
Wonchae
W
Kim
Sung Soo
SS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D021984:Cyclophilin A / Q000096:biosynthesis* / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D021984:Cyclophilin A; D002945:Cisplatin