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Effects of eicosapentaenoic acid and the GPR120 agonist TUG‐891 on lysophosphatidic acid signaling in human prostate cancer cells (1066.10)
Author(s) -
Hopkins Mandi,
Liu Ze,
Meier Kathryn
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1066.10
Subject(s) - prostate cancer , du145 , eicosapentaenoic acid , gpr120 , lysophosphatidic acid , free fatty acid receptor 1 , cancer research , agonist , receptor , endocrinology , cancer , apoptosis , medicine , g protein coupled receptor , prostate , chemistry , lncap , biochemistry , fatty acid , polyunsaturated fatty acid
There is a high incidence of prostate cancer in the Western world, which may be partially attributed to Western diets that are generally deficient in omega‐3 fatty acids (n‐3 FAs). Dietary n‐3 FAs have been shown to inhibit proliferation of prostate cancer cells in culture. The G protein‐coupled receptor GPR120, which is expressed in normal prostate and prostate tumors, serves as a receptor for the n‐3 FA eicosapentaenoic acid (EPA). We therefore hypothesized that the inhibitory effects of n‐3 FAs on prostate cancer cell proliferation are mediated by GPR120. To test this hypothesis, we performed proliferation and signal transduction studies, comparing the effects of lysophosphatidic acid (LPA), EPA, the GPR120 agonist TUG‐891, and the GPR40 agonist GW9508 in DU145 and PC‐3 cells. We found that EPA and TUG‐891 inhibit proliferation of human prostate cancer cells in response to LPA. In addition, brief (15 minute) pre‐incubation of serum‐starved cells with EPA or TUG‐891 suppresses subsequent activation of ERK, p70S6K, and FAK in response to LPA. This rapid effect of EPA is consistent with mediation by a GPCR. Our data suggest that GPR120 shows promise as a therapeutic target in prostate cancer. Grant Funding Source : Washington State University College of Pharmacy