title: Role of eicosanoids in prostate cancer progression.
abstract: Metabolism of arachidonic acid through cyclooxygenase, lipoxygenase, or P450 epoxygenase pathways leads to the formation of various bioactive eicosanoids. In this review, we discuss alterations in expression pattern of eicosanoid-generating enzymes found during prostate tumor progression and expound upon their involvement in tumor cell proliferation, apoptosis, motility, and tumor angiogenesis. The expression of cyclooxygenase-2, 12-lipoxygenase, and 15-lipoxygenase-1 are up-regulated during prostate cancer progression. It has been demonstrated that inhibitors of cyclooxygenase-2, 5-lipoxygenase and 12-lipoxygenase cause tumor cell apoptosis, reduce tumor cell motility and invasiveness, or decrease tumor angiogenesis and growth. The eicosanoid product of 12-lipoxygenase, 12(S)-hydroeicosatetraenoic acid, is found to activate Erkl/2 kinases in LNCaP cells and PKCalpha in rat prostate AT2.1 tumor cells. Overexpression of 12-lipoxygenase and 15-lipoxygenase-1 in prostate cancer cells stimulate prostate tumor angiogenesis and growth, suggesting a facilitative role for 12-lipoxygenase and 15-lipoxygenase-1 in prostate tumor progression. The expression of 15-lipoxygenase-2 is found frequently to be lost during the initiation and progression of prostate tumors. 15(S)-hydroxyeicosatetraenoic acid, the product of 15-lipoxygenase-2, inhibits proliferation and causes apoptosis in human prostate cancer cells, suggesting an inhibitory role for 15-lipoxygenase-2 in prostate tumor progression. The regulation of prostate cancer progression by eicosanoids, in either positive or negative ways, provides an exciting possibility for management of this disease.
authors.affiliation: Department of Radiation Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, MI 48202, USA.
authors.forename: D
authors.initials: D
authors.lastname: Nie
authors.forename: M
authors.initials: M
authors.lastname: Che
authors.forename: D
authors.initials: D
authors.lastname: Grignon
authors.forename: K
authors.initials: K
authors.lastname: Tang
authors.forename: K V
authors.initials: KV
authors.lastname: Honn
mesh_terms: D017209:Apoptosis; D016718:Arachidonic Acid / Q000378:metabolism; D018890:Chemoprevention; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D018450:Disease Progression; D015777:Eicosanoids / Q000502:physiology*; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*
chemical_list: D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D016718:Arachidonic Acid; D008084:Lipoxygenase