Abstract 5583: Differential effect of phenethyl isothiocyanate on expression of antioxidant defense genes between normal and cancerous human prostate cells

Abstract

Abstract Phenethyl isothiocyanate (PEITC) is a promising cancer chemopreventive constituent of cruciferous vegetables (e.g., watercress) as evidenced by efficacy against chemically-induced cancer in experimental rodents. The PEITC is also empowered to inhibit growth of cultured and xenografted human prostate cancer cells, which correlates with apoptotic and autophagic cell death. We have shown previously that reactive oxygen species (ROS) play a critical role in proapoptotic signal transduction by PEITC in human prostate cancer cells. Interestingly, a representative normal human prostate epithelial cell line (PrEC) is significantly more resistant to PEITC-induced apoptosis compared with cancerous prostate cells including PC-3 and LNCaP. However, the mechanism behind this differential response remains elusive. The present study was undertaken to test a hypothesis that differential sensitivity of normal versus cancerous human prostate cells to PEITC-mediated proapoptotic response is determined by differences in ROS production and/or basal or inducible expression of antioxidant defense genes. The PEITC treatment resulted in ROS production in PC-3 human prostate cancer cells as judged by flow cytometry and fluorescence microscopy using a chemical probe (MItoSOX Red) and EPR using a cell permeable sin probe (1-hydroxy-3-methoxy-carbonyl-2,2,5,5-tetramethylpyrrolidine). These effects were not observed in PrEC cells similarly treated with the PEITC. Basal antioxidant defense gene expression signature was strikingly different between PC-3 and PrEC cells. Moreover, PEITC treatment (2.5 μM, 6 h) caused up-regulation of 29 genes and down-regulation of 2 genes in PC-3 cells. Conversely only 4 genes were up-regulated and 10 genes were down-regulated by a similar PEITC treatment in the PrEC cell line. The results of the present study clearly indicate that differential sensitivity of PC-3 versus PrEC cells to proapoptotic effect of PEITC is likely attributable to both differences in ROS production and basal as well as altered expression of antioxidant defense genes. This investigation was supported by the USPHS grant CA101753-07, awarded by the National Cancer Institute. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5583. doi:10.1158/1538-7445.AM2011-5583