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Cancer Invest ; 26(7): 708-17, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18608213

ABSTRACT

Farnesol (FOH) and geranylgeraniol (GGOH) possess anti-tumor potential, while peroxisome proliferator-activated receptor gamma (PPARgamma) 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 PPARgamma 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 PPARgamma promoter activity. Pretreatment of the PPARgamma antagonist GW9662 reduces FOH-induced growth inhibition and the associated PARP cleavage. We conclude that PPARgamma activation is essential to elicit the anti-carcinogenic action of herbal isoprenols in colonic cancer cells.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Colonic Neoplasms/metabolism , Diterpenes/pharmacology , Farnesol/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , PPAR gamma/agonists , Transcriptional Activation/drug effects , Anilides/pharmacology , Caspase 3/metabolism , Cell Proliferation/drug effects , Cell Survival/drug effects , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Dose-Response Relationship, Drug , Enzyme Activation , HCT116 Cells , HT29 Cells , Humans , Inhibitor of Apoptosis Proteins , Microtubule-Associated Proteins/metabolism , Neoplasm Proteins/metabolism , PPAR gamma/genetics , PPAR gamma/metabolism , Poly(ADP-ribose) Polymerases/metabolism , Promoter Regions, Genetic/drug effects , Survivin , Time Factors , bcl-X Protein/metabolism
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