Role of eicosanoids in prostate cancer progression

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

Research output: Contribution to journalReview article

92 Scopus citations

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 PKCα 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.

Original languageEnglish (US)
Pages (from-to)195-206
Number of pages12
JournalCancer and Metastasis Reviews
Volume20
Issue number3-4
DOIs
StatePublished - Jan 1 2001

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Keywords

  • Apoptosis
  • Cyclooxygenase
  • Eicosanoid
  • Lipoxygenase
  • Tumor metastasis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Nie, D., Che, M., Grignon, D., Tang, K., & Honn, K. V. (2001). Role of eicosanoids in prostate cancer progression. Cancer and Metastasis Reviews, 20(3-4), 195-206. https://doi.org/10.1023/A:1015579209850