15-lipoxygenase metabolites of docosahexaenoic acid inhibit prostate cancer cell proliferation and survival. PLoS One 2012;7(9):e45480
Date
10/03/2012Pubmed ID
23029040Pubmed Central ID
PMC3447860DOI
10.1371/journal.pone.0045480Scopus ID
2-s2.0-84866673758 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
A 15-LOX, it is proposed, suppresses the growth of prostate cancer in part by converting arachidonic, eicosatrienoic, and/or eicosapentaenoic acids to n-6 hydroxy metabolites. These metabolites inhibit the proliferation of PC3, LNCaP, and DU145 prostate cancer cells but only at ≥1-10 µM. We show here that the 15-LOX metabolites of docosahexaenoic acid (DHA), 17-hydroperoxy-, 17-hydroxy-, 10,17-dihydroxy-, and 7,17-dihydroxy-DHA inhibit the proliferation of these cells at ≥0.001, 0.01, 1, and 1 µM, respectively. By comparison, the corresponding 15-hydroperoxy, 15-hydroxy, 8,15-dihydroxy, and 5,15-dihydroxy metabolites of arachidonic acid as well as DHA itself require ≥10-100 µM to do this. Like DHA, the DHA metabolites a) induce PC3 cells to activate a peroxisome proliferator-activated receptor-γ (PPARγ) reporter, express syndecan-1, and become apoptotic and b) are blocked from slowing cell proliferation by pharmacological inhibition or knockdown of PPARγ or syndecan-1. The DHA metabolites thus slow prostate cancer cell proliferation by engaging the PPARγ/syndecan-1 pathway of apoptosis and thereby may contribute to the prostate cancer-suppressing effects of not only 15-LOX but also dietary DHA.
Author List
O'Flaherty JT, Hu Y, Wooten RE, Horita DA, Samuel MP, Thomas MJ, Sun H, Edwards IJAuthor
Michael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ApoptosisArachidonate 15-Lipoxygenase
Caspases
Cell Line, Tumor
Cell Proliferation
Cell Survival
Docosahexaenoic Acids
Humans
Male
PPAR gamma
Prostatic Neoplasms
Signal Transduction
Syndecan-1
