Cancer and Metastasis Reviews

, Volume 20, Issue 3–4, pp 195–206 | Cite as

Role of Eicosanoids in Prostate Cancer Progression

  • Daotai Nie
  • Mingxin Che
  • David Grignon
  • Keqin Tang
  • Kenneth V. Honn
Article

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-l 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 PKCα in rat prostate AT2.1 tumor cells. Overexpression of 12-lipoxygenase and 15-lipoxygenase-l in prostate cancer cells stimulate prostate tumor angiogenesis and growth, suggesting a facilitative role for 12-lipoxygenase and 15-lipoxygenase-l 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.

eicosanoid cyclooxygenase lipoxygenase tumor metastasis apoptosis 

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Daotai Nie
    • 1
  • Mingxin Che
    • 2
  • David Grignon
    • 2
  • Keqin Tang
    • 1
  • Kenneth V. Honn
    • 1
    • 2
  1. 1.Department of Radiation OncologyWayne State University School of Medicine and Karmanos Cancer InstituteDetroitUSA
  2. 2.Department of PathologyWayne State University School of Medicine and Karmanos Cancer InstituteDetroitUSA

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