Increased Nox1 and hydrogen peroxide in prostate cancer

Abstract

BACKGROUND Reactive oxygen species (ROS) are emerging as candidate mediators of growth and angiogenesis in cancer. Increased ROS often correlates with cell growth, e.g., Ras-transformed cells and cells treated with growth factors. While non-transformed cells respond to growth factors/cytokines with the regulated production of ROS, tumor cells in culture frequently overproduce H₂O_2. We propose that NADPH oxidases (Nox) account for increased levels of ROS in some cancers. Previously, transfection of Nox1 into a prostate cancer cell line dramatically enhanced tumor growth (Arbiser et al.: PNAS 99:715–720, 2001). METHODS Using immunohistochemistry, immunofluorescence, dihydroethidium staining, and Flow cytometry, we investigated the correlation between Nox1 and ROS in prostate cancer. RESULTS Here, we demonstrate that human prostate tumors show increased H₂O₂ levels. Furthermore, 80% of human prostate tumor samples show markedly increased Nox1 protein levels and increased mRNA levels. In addition, a series of cell lines developed from LNCaP prostate cancer cells that demonstrate increasing tumor and metastatic potential, show increased Nox1 and a parallel increase in H₂O₂ levels. CONCLUSIONS The results illustrate that human prostate cancer frequently show both increased H₂O₂ and Nox1, and that in an animal model system increased Nox1/H₂O₂ correlates with increased tumorigenicity.