Eicosanoid Regulation of Angiogenesis in Human Prostate Carcinoma and Its Therapeutic Implications

: Cancer of the prostate is the most commonly diagnosed cancer in America. There are several lines of evidence implicating the involvement of arachidonate 12-lipoxygenase, an enzyme metabolizing arachidonic acid to form 12(S)-hydroxyeicosatetraenoic acid (HETE), in prostate cancer progression. First, as prostate cancer reaches a more advanced stage, the level of 12-lipoxygenase expression is increased. Second, overexpression of 12-lipoxygenase in human prostate cancer cells stimulates angiogenesis and tumor growth. Third, an inhibitor of 12-lipoxygenase has been found effective against metastatic prostate tumor growth, and the inhibition of 12-lipoxygenase is related with the reduction of tumor angiogenesis. Collectively, these studies suggest that 12-lipoxygenase regulates tumor angiogenesis in prostate cancer and that inhibition of 12-lipoxygenase is a novel therapeutic approach for the treatment of prostate cancers.