PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs.

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He TC, Chan TA, Vogelstein B, Kinzler KW

PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs.

Cell. 1999 Oct 29;99(3):335-45.

PubMed ID

10555149 [ View in PubMed

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Abstract

PPARB was identified as a target of APC through the analysis of global gene expression profiles in human colorectal cancer (CRC) cells. PPARdelta expression was elevated in CRCs and repressed by APC in CRC cells. This repression was mediated by beta-catenin/Tcf-4-responsive elements in the PPARdelta promotor. The ability of PPARs to bind eicosanoids suggested that PPARdelta might be a target of chemopreventive non-steroidal anti-inflammatory drugs (NSAIDs). Reporters containing PPARdelta-responsive elements were repressed by the NSAID sulindac. Furthermore, sulindac was able to disrupt the ability of PPARdelta to bind its recognition sequences. These findings suggest that NSAIDs inhibit tumorigenesis through inhibition of PPARdelta, the gene for which is normally regulated by APC.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Sulindac	Peroxisome proliferator-activated receptor delta	Protein	Humans	Unknown	Negative modulator	Details