Abstract
The effects of several cancer chemotherapeutic drugs and radiation are mediated, at least in part, by oxidative stress. To better understand this process, we analyzed certain biochemical properties affecting reduction-oxidation (redox) balance in normal prostate epithelial cells and several prostate cancer cell lines. Highly aggressive androgen-independent prostate cancer PC3 cells demonstrated significantly higher levels of total antioxidant capacity (AC) and intra- and extracellular glutathione (GSH)/glutathione disulfide (GSSG) ratios when compared with normal prostate epithelial PrEC cells. WPE1-NB26 cells, a prostate cancer cell line derived from immortalized RWPE1 human prostate epithelial cells, demonstrated significantly higher levels of total AC and intra- and extracellular GSH/GSSG ratios, but lower levels of intracellular reactive oxygen/nitrogen species and lipid peroxidation compared with RWPE1 cells. LNCaP-C4-2 cells, a more aggressive prostate cancer derived from less aggressive androgen-responsive LNCaP cells, exhibited higher levels of AC and extracellular GSH/GSSG ratio when compared to LNCaP cells. Specific cell types showed distinct cytotoxic responses to redox-modulating compounds. WPE1-NB26 cells were more sensitive to phenethyl isothiocyanate and tumor necrosis factor (TNF) than RWPE1 cells, while PC3 cells were more sensitive to TNF than PrEC cells. These results are consistent with the hypothesis that cancer cell redox state may modulate responses to redox-modulating therapeutic regimens.
Highlights
The term cellular redox state refers to the balance between oxidizing and reducing equivalents in the cell
Recent studies in our laboratory demonstrated that modulation of extracellular redox state of a prostate cancer cell line by overexpression of extracellular SOD (EC-SOD) resulted in inhibition of cell invasion and decreased matrix metalloproteinase (MMP) and membrane type 1 MMP (MT1-MMP)
The present study focused on intra- and extracellular redox states in normal/immortalized prostate epithelial cells and specific prostate cancer cell lines
Summary
The term cellular redox state refers to the balance between oxidizing and reducing equivalents in the cell. Recent studies in our laboratory demonstrated that modulation of extracellular redox state of a prostate cancer cell line by overexpression of EC-SOD resulted in inhibition of cell invasion and decreased matrix metalloproteinase (MMP) and membrane type 1 MMP (MT1-MMP). Inhibition of cell invasion was demonstrated to occur in aggressive prostate cancer WPE1-NB26 cells, but not immortalized RWPE1 human prostate epithelial cells [20] These results suggest that there are shifts in intra- and extracellular redox states as cancer progresses to a more aggressive state. Our findings provide new insights into the possible usefulness or dangers of prooxidant or antioxidant agents as cancer therapeutic drugs; therapeutic results with these compounds will depend on the specific intra- and extracellular redox biochemistries of the cancer cell type that is the target of therapy
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