15-lipoxygenase-1 in colorectal cancer: a review

Tumour Biol. 2009;30(4):185-99. doi: 10.1159/000236864. Epub 2009 Sep 10.

Abstract

Objective: Enzymes involved in the oxidative metabolism of n-6 polyunsaturated fatty acids, like lipoxygenase (LOX) and cyclooxygenase (COX), are significant in the pathogenesis of colorectal cancer. Of these enzymes, 15-LOX-1 is expressed in colon. Aim of this article is to describe the role and regulation of 15-LOX-1 in colorectal cancer and highlight its importance in cancer therapeutics.

Methods: For our electronic literature research in PubMed and MEDLINE, key words related to 15-LOX-1 and colorectal cancer were used to find articles for this review.

Results: From the evidences, we believe that 15-LOX-1 has anti-carcinogenic effects in colorectal cancer, dependent or independent of its metabolites, and is manifested through downstream pathways involving cGMP, PPAR, p53, p21 and NAG-1, increasing apoptosis and decreasing proliferation in cancer cells. Regulation of 15-LOX-1 expression is achieved at transcription level by global histone acetylation and may also be dependent on GATA-6, IL-4 and IL-13. Positive relationship exists between 15-LOX-1 and survival in colorectal cancer.

Conclusion: Evidences strongly support that therapeutic modulation of 15-LOX-1 may be a key to the treatment of colorectal cancer. However, it is still undecided whether the up-regulation of 15-LOX-1 alone can be sufficient to treat colorectal cancer and further studies are awaited.

Publication types

  • Review

MeSH terms

  • Adenoma / enzymology
  • Adenoma / metabolism
  • Animals
  • Anticarcinogenic Agents / blood
  • Anticarcinogenic Agents / metabolism
  • Arachidonate 15-Lipoxygenase / biosynthesis
  • Arachidonate 15-Lipoxygenase / blood
  • Arachidonate 15-Lipoxygenase / genetics
  • Arachidonate 15-Lipoxygenase / metabolism*
  • Arachidonic Acid / metabolism
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / metabolism
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • Disease Models, Animal
  • GATA6 Transcription Factor / metabolism
  • Humans
  • Intestinal Mucosa / enzymology
  • Intestinal Mucosa / metabolism
  • PPAR alpha / metabolism
  • PPAR delta / metabolism
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • PPAR-beta / metabolism
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Anticarcinogenic Agents
  • GATA6 Transcription Factor
  • PPAR alpha
  • PPAR delta
  • PPAR gamma
  • PPAR-beta
  • Arachidonic Acid
  • ALOX15B protein, human
  • Arachidonate 15-Lipoxygenase
  • Cyclic GMP-Dependent Protein Kinases