Herbal Isoprenols Induce Apoptosis in Human Colon Cancer Cells Through Transcriptional Activation of PPARγ

Abstract

Farnesol (FOH) and geranylgeraniol (GGOH) possess anti-tumor potential, while peroxisome proliferator-activated receptor γ (PPARγ) has exhibited modulating effects in colorectal cancers. We investigated the anti-carcinogenic effects of these isoprenols in HT-29 and HCT116 colon cancer cells and PPARγ involvement. Results indicate that the FOH- and GGOH-induced apoptosis involve caspase 3 activation, PARP cleavage, nuclear chromatin condensation, down-regulation of Bcl-x_L and survivin expression, with increased PPARγ promoter activity. Pretreatment of the PPARγ antagonist GW9662 reduces FOH-induced growth inhibition and the associated PARP cleavage. We conclude that PPARγ activation is essential to elicit the anti-carcinogenic action of herbal isoprenols in colonic cancer cells.

Keywords:

• FOH
• GGOH
• HT-29 cells
• HCT116 cells
• PPARγ
• GW9662