Abstract 2072: Distinct antioxidant profiles of human prostate carcinoma cell lines and tissues: Implications for rational design of redox therapy

Abstract

Abstract Several cancer chemotherapeutic drugs and radiation mediate their effects, at least in part, by generation of reactive oxygen/nitrogen species. Therefore, the levels of antioxidants and status of cellular redox state have tremendous influence on the outcome of these therapies. We analyzed antioxidant proteins in normal prostate epithelial cells and tissues as well as prostate cancer cell lines and tissues. Highly aggressive androgen-independent prostate cancer PC3 and LNCAP-C42B cells demonstrated significantly higher levels of superoxide dismutase (SOD) 2, peroxyredoxin (Prx) 1, 2, 3, and 4, thioredoxin (Trx) 1 and 2, and thioredoxin reductase (TR) 1 and 2, relative to normal prostate epithelial PrEC cells and immortalized RWPE1 human prostate epithelial cells. Similarity, the highly aggressive human prostate cancer tissues (Gleason scores 4+4 and 4+5) demonstrated significantly higher levels of SOD1 and 2, Prx 3 and 4, Trx 1 and 2, and TR 1 and 2 relative to adjacent normal prostate tissues. In contrast, the expression levels of these antioxidant proteins were lower or were not altered in less aggressive human prostate cancer tissues (Gleason score 3+3) relative to adjacent normal prostate tissues. Utilizing Trx1 redox western as a marker of cellular redox states, we found more oxidized form of Trx1 in PC3 and LNCAP-C42B cells and human prostate cancer tissues (Gleason scores 4+4 and 4+5) despite their higher levels of Trx1 protein expression. Our data suggest that alteration in antioxidant proteins and cellular redox state may differentiate cancers from non-cancer tissues. Additionally, knowledge of redox state profiles can help to predict the response of each cancer cell type to chemotherapeutic drugs and radiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2072. doi:1538-7445.AM2012-2072