PPARγ1 as a molecular target of eicosapentaenoic acid in human colon cancer (HT-29) cells

Clinton D. Allred, Dominique R. Talbert, R. Chase Southard, Xin Wang, Michael W. Kilgore

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

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 PPARγ1 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 PPARγ antagonist, significantly inhibited this effect, whereas overexpressing the receptor enhanced it. EPA also stimulated the PPRE reporter in a PPARγ negative cancer cell line (22Rv1) when the cells were cotransfected with a PPARγ1 expression plasmid and this effect was again inhibited by GW. Furthermore, in vitro incubation of EPA with PPARγ1 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 PPARγ. 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 PPARγ. 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 PPARγ activation. These studies identify PPARγ as a molecular mediator of (n-3) PUFA actions in colon cancer cells.

Original languageEnglish
Pages (from-to)250-256
Number of pages7
JournalJournal of Nutrition
Volume138
Issue number2
DOIs
StatePublished - Feb 2008

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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