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Cancer and Metastasis Reviews

, 26:503 | Cite as

Lipoxygenase metabolism: roles in tumor progression and survival

  • Graham P. Pidgeon
  • Joanne Lysaght
  • Sriram Krishnamoorthy
  • John V. Reynolds
  • Ken O’Byrne
  • Daotai Nie
  • Kenneth V. Honn
Article

Abstract

The metabolism of arachidonic acid through lipoxygenase pathways leads to the generation of various biologically active eicosanoids. The expression of these enzymes vary throughout the progression of various cancers, and thereby they have been shown to regulate aspects of tumor development. Substantial evidence supports a functional role for lipoxygenase-catalyzed arachidonic and linoleic acid metabolism in cancer development. Pharmacologic and natural inhibitors of lipoxygenases have been shown to suppress carcinogenesis and tumor growth in a number of experimental models. Signaling of hydro[peroxy]fatty acids following arachidonic or linoleic acid metabolism potentially effect diverse biological phenomenon regulating processes such as cell growth, cell survival, angiogenesis, cell invasion, metastatic potential and immunomodulation. However, the effects of distinct LOX isoforms differ considerably with respect to their effects on both the individual mechanisms described and the tumor being examined. 5-LOX and platelet type 12-LOX are generally considered pro-carcinogenic, with the role of 15-LOX-1 remaining controversial, while 15-LOX-2 suppresses carcinogenesis. In this review, we focus on the molecular mechanisms regulated by LOX metabolism in some of the major cancers. We discuss the effects of LOXs on tumor cell proliferation, their roles in cell cycle control and cell death induction, effects on angiogenesis, migration and the immune response, as well as the signal transduction pathways involved in these processes. Understanding the molecular mechanisms underlying the anti-tumor effect of specific, or general, LOX inhibitors may lead to the design of biologically and pharmacologically targeted therapeutic strategies inhibiting LOX isoforms and/or their biologically active metabolites, that may ultimately prove useful in the treatment of cancer, either alone or in combination with conventional therapies.

Keywords

Lipoxygenase Tumor survival Apoptosis Angiogenesis Immune suppression 

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Graham P. Pidgeon
    • 1
    • 6
  • Joanne Lysaght
    • 2
  • Sriram Krishnamoorthy
    • 3
  • John V. Reynolds
    • 1
  • Ken O’Byrne
    • 4
  • Daotai Nie
    • 5
  • Kenneth V. Honn
    • 3
  1. 1.Department of Clinical SurgeryTrinity College Dublin, St. James HospitalDublin 8Ireland
  2. 2.Department of HaematologyTrinity College Dublin, St. James HospitalDublin 8Ireland
  3. 3.Department of PathologyWayne State University School of Medicine & Karmanos Cancer InstituteDetroitUSA
  4. 4.Department of Clinical MedicineTrinity College Dublin, St. James HospitalDublin 8Ireland
  5. 5.Department of Medical Microbiology, Immunology, and Cell BiologySouthern Illinois University School of Medicine and Cancer InstituteSpringfieldUSA
  6. 6.Department of Clinical Surgery, Institute of Molecular MedicineTrinity Center for Health Sciences, TCD/St. James’s HospitalDublin 8Ireland

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