15-lipoxygenase-1 in colorectal cancer: a review.
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.


CONCLUSIONS
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.
Bhattacharya
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Department of General Surgery, George Eliot Hospital, Nuneaton, UK. Sayantan.Bhattacharya@geh.nhs.uk
Mathew
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G
Jayne
D G
DG
Pelengaris
S
S
Khan
M
M
D000236:Adenoma / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D016588:Anticarcinogenic Agents / Q000097:blood / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D004195:Disease Models, Animal; D050993:GATA6 Transcription Factor / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism; D047494:PPAR delta / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D048068:PPAR-beta / Q000378:metabolism; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016588:Anticarcinogenic Agents; D050993:GATA6 Transcription Factor; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D048068:PPAR-beta; D016718:Arachidonic Acid; C458528:ALOX15B protein, human; D001093:Arachidonate 15-Lipoxygenase; D017869:Cyclic GMP-Dependent Protein Kinases