Differential response of normal (PrEC) and cancerous human prostate cells (PC-3) to phenethyl isothiocyanate-mediated changes in expression of antioxidant defense genes.

PURPOSE: The present study was undertaken to test a hypothesis that differential sensitivity of normal and cancerous human prostate cells to prooxidant effect of phenethyl isothiocyanate (PEITC) is determined by altered expression of antioxidant defense genes.
METHODS: Prooxidant effect of PEITC was assessed by flow cytometry using a chemical probe and measurement of hydrogen peroxide production. Gene expression was determined by real-time PCR using Human Oxidative Stress and Antioxidant Defense RT(2) Profiler™. Protein expression was determined by Western blotting.
RESULTS: The PEITC treatment resulted in generation of reactive oxygen species and hydrogen peroxide production in PC-3 human prostate cancer cells but not in a representative normal human prostate epithelial cell line (PrEC). Basal oxidative stress-antioxidant defense gene expression signature was strikingly different between PC-3 and PrEC cells. The PEITC treatment (2.5 μM, 6 h) caused up-regulation of 29 genes and down-regulation of 2 genes in PC-3 cells. Conversely, 4 genes were up-regulated, and 10 genes were down-regulated by a similar PEITC treatment in the PrEC cell line.
CONCLUSIONS: Differential sensitivity of PC-3 versus PrEC cells to prooxidant effect of PEITC is likely attributable to difference in basal as well as altered expression of antioxidant defense genes.