Journal
JOURNAL OF NUTRITION
Volume 138, Issue 2, Pages 250-256Publisher
AMER SOC NUTRITIONAL SCIENCE
DOI: 10.1093/jn/138.2.250
Keywords
-
Categories
Funding
- NCI NIH HHS [R01-CA-95609] Funding Source: Medline
- NCRR NIH HHS [P20-RR15592] Funding Source: Medline
- NIDA NIH HHS [5-K12-DA-14040-02] Funding Source: Medline
Ask authors/readers for more resources
Diets high in (n-3) PUFA decrease colon cancer development and suppress colon tumor growth, but the molecular mechanism through which these compounds act is largely unknown. We sought to determine whether PPAR gamma 1 serves as a molecular link between the physiological actions of eicosapentaenoic acid (EPA) in human colon cancer cells (HT-29). At nutritionally relevant concentrations, EPA stimulated a PPAR response element (PPRE) reporter assay in a dose-responsive manner in HT-29 cells. Cotreatment with GW9662 (GW), a PPAR gamma antagonist, significantly inhibited this effect, whereas overexpressing the receptor enhanced it. EPA also stimulated the PPRE reporter in a PPAR gamma negative cancer cell line (22Rv1) when the cells were cotransfected with a PPAR gamma 1 expression plasmid and this effect was again inhibited by GW. Furthermore, in vitro incubation of EPA with PPAR gamma 1 enhanced binding of the protein to DNA containing a PPRE. Next, we sought to determine whether EPA or a prostaglandin formed from EPA is the functional ligand of PPAR gamma. Cotreatment in HT-29 and 22Rv1 cells with EPA and acetyl salicylic acid, an inhibitor of cyclooxygenase activity, activated the PPRE reporter at levels similar to EPA alone, suggesting that EPA itself is a ligand of PPAR gamma. Finally, EPA suppressed HT-29 cell growth and this effect was significantly reversed by the addition of GW, suggesting that in part the physiological actions of EPA are the result of PPAR gamma activation. These studies identify PPAR gamma as a molecular mediator of (n-3) PUFA actions in colon cancer cells. J. Nutr. 138: 250-256, 2008.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available