Lipoxygenase inhibition in prostate cancer.
Multiple population-based studies show an increased risk of prostate cancer in populations that consume large amounts of animal fat. However, the molecular mechanisms linking dietary fat to prostate cancer biology remain obscure. Animal fats are typically rich sources of arachidonic acid and this fatty acid is converted to a wide range of powerful compounds including leukotrienes, prostaglandins, etc. We have shown that PC3 and LNCaP convert arachidonic acid to the 5-lipoxygenase product, 5-HETE. When the formation of 5-HETE is blocked, human prostate cancer cells enter apoptosis in less than 1 h and are dead within 2 h. Exogenous 5-HETE can rescue these cancer cells. These findings indicate that 5-HETE is a potent survival factor for human prostate cancer cells.
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002630:Chemotactic Factors / Q000378:metabolism*; D004041:Dietary Fats / Q000009:adverse effects*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000209:etiology / Q000517:prevention & control*; D012680:Sensitivity and Specificity