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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
17
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pubmed:dateCreated |
2003-8-20
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pubmed:abstractText |
Diminished apoptosis, a critical event in tumorigenesis, is linked to down-regulated 15-lipoxygenase-1 (15-LOX-1) expression in colorectal cancer cells. 13-S-hydroxyoctadecadienoic acid (13-S-HODE), which is the primary product of 15-LOX-1 metabolism of linoleic acid, restores apoptosis. Nonsteroidal antiinflammatory drugs (NSAIDs) transcriptionally up-regulate 15-LOX-1 expression to induce apoptosis. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors for linoleic and arachidonic acid metabolites. PPAR-delta promotes colonic tumorigenesis. NSAIDs suppress PPAR-delta activity in colon cancer cells. The mechanistic relationship between 15-LOX-1 and PPAR-delta was previously unknown. Our current study shows that (i) 13-S-HODE binds to PPAR-delta, decreases PPAR-delta activation, and down-regulates PPAR-delta expression in colorectal cancer cells; (ii) the induction of 15-LOX-1 expression is a critical step in NSAID down-regulation of PPAR-delta and the resultant induction of apoptosis; and (iii) PPAR-delta is an important signaling receptor for 13-S-HODE-induced apoptosis. The in vivo relevance of these mechanistic findings was demonstrated in our tumorigenesis studies in nude mouse xenograft models. Our findings indicate that the down-regulation of PPAR-delta by 15-LOX-1 through 13-S-HODE is an apoptotic signaling pathway that is activated by NSAIDs.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-10198642,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-10506115,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-10555149,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-10866668,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-10874062,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-10904086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-11048733,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-11087869,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-11156377,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-11226285,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-11357141,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-11729302,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-11832206,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-11861401,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-1324435,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-7479951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-7606732,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-7615821,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-7706406,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-8385741,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-9102217,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-9177185,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-9435691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12909723-9514791
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/13-hydroxy-9,11-octadecadienoic acid,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonate 15-Lipoxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Linoleic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/celecoxib
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
100
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9968-73
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:12909723-Animals,
pubmed-meshheading:12909723-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:12909723-Apoptosis,
pubmed-meshheading:12909723-Arachidonate 15-Lipoxygenase,
pubmed-meshheading:12909723-Base Sequence,
pubmed-meshheading:12909723-Colorectal Neoplasms,
pubmed-meshheading:12909723-Down-Regulation,
pubmed-meshheading:12909723-Humans,
pubmed-meshheading:12909723-Linoleic Acids,
pubmed-meshheading:12909723-Mice,
pubmed-meshheading:12909723-Mice, Nude,
pubmed-meshheading:12909723-Models, Biological,
pubmed-meshheading:12909723-Neoplasm Transplantation,
pubmed-meshheading:12909723-Protein Binding,
pubmed-meshheading:12909723-Pyrazoles,
pubmed-meshheading:12909723-RNA, Neoplasm,
pubmed-meshheading:12909723-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:12909723-Signal Transduction,
pubmed-meshheading:12909723-Sulfonamides,
pubmed-meshheading:12909723-Transcription Factors,
pubmed-meshheading:12909723-Transfection,
pubmed-meshheading:12909723-Transplantation, Heterologous,
pubmed-meshheading:12909723-Tumor Cells, Cultured,
pubmed-meshheading:12909723-Up-Regulation
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pubmed:year |
2003
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pubmed:articleTitle |
The 15-lipoxygenase-1 product 13-S-hydroxyoctadecadienoic acid down-regulates PPAR-delta to induce apoptosis in colorectal cancer cells.
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pubmed:affiliation |
Departments of Clinical Cancer Prevention, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ishureiqi@mdanderson.org
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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