PKCδ activation mediates angiogenesis via NADPH oxidase activity in PC-3 prostate cancer cells.

BACKGROUND: PKCδ is generally known as a pro-apoptotic and anti-proliferative enzyme in human prostate cancer cells. METHODS: Here, we investigated the role of PKCδ on the growth of PC-3 human prostate cancer cells in vivo and in vitro. RESULTS: We found that sustained treatment with a specific PKCδ activator (ψδ receptor for active C kinase, ψδRACK) increased growth of PC-3 xenografts. There was increased levels of HIF-1α, vascular endothelial growth factor and CD31-positive cells in PC-3 xenografts, representative of increased tumor angiogenesis. Mechanistically, PKCδ activation increased the levels of reactive oxygen species (ROS) by binding to and phosphorylating NADPH oxidase, which induced its activity. Also, PKCδ-induced activation of NADPH oxidase increased the level of HIF-1α. CONCLUSIONS: Our results using tumors from the PC-3 xenograft model suggest that PKCδ activation increases angiogenic activity in androgen-independent PC-3 prostate cancer cells by increasing NADPH oxidase activity and HIF-1α levels and thus may partly be responsible for increased angiogenesis in advanced prostate cancer.