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Life sciences

A natural propenoic acid derivative activates peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta).


PMID 20153754

Abstract

Previous studies showed that natural prenyloxyphenylpropanoid derivatives have potent biological properties in vivo. Given the structural similarities between these compounds and known peroxisome proliferator-activated receptor (PPAR) agonists, the present study examined the hypothesis that propenoic acid derivatives activate PPARs. Chimeric reporter assays were performed to identify propenoic acid derivates that could activate PPARs. Quantitative polymerase chain reaction (qPCR) analysis of wild-type and Pparbeta/delta-null mouse primary keratinocytes was performed to determine if a test compound could specifically activate PPARbeta/delta. A human epithelial carcinoma cell line and primary mouse keratinocytes were used to determine the effect of the compound on cell proliferation. Three of the propenoic acid derivatives activated PPARs, with the greatest efficacy being observed with prenyloxycinnamic acid derivatives 4'-geranyloxyferulic acid (compound 1) for PPARbeta/delta. Compound 1 increased expression of a known PPARbeta/delta target gene through a mechanism that requires PPARbeta/delta. Inhibition of cell proliferation by compound 1 was found in a human epithelial carcinoma cell line. Results from these studies demonstrate that compound 1 can activate PPARbeta/delta and inhibit cell proliferation of a human skin cancer cell line, suggesting that the biological effects of 4'-geranyloxyferulic acid may be mediated in part by activating this PPAR isoform.

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