Herbal isoprenols induce apoptosis in human colon cancer cells through transcriptional activation of PPARgamma.
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.
Au-Yeung
Kathy Ka-Wai
KK
Pharmacology and Toxicology Laboratory, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
Liu
Po-Ling
PL
Chan
Cecilia
C
Wu
Wing-Yee
WY
Lee
Susanna Sau-Tuen
SS
Ko
Joshua Ka-Shun
JK
D000813:Anilides / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005204:Farnesol / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D000077022:Survivin; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects*; D051020:bcl-X Protein / Q000378:metabolism
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000972:Antineoplastic Agents, Phytogenic; C494811:BCL2L1 protein, human; C107489:BIRC5 protein, human; D004224:Diterpenes; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D047495:PPAR gamma; D000077022:Survivin; D051020:bcl-X Protein; D005204:Farnesol; C017338:geranylgeraniol; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3