Peroxisome proliferator-activated receptor-gamma agonists cause growth arrest and apoptosis in human ovarian carcinoma cell lines.
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. PPARgamma agonists inhibit the growth of many types of cancers. To our knowledge, the effect of PPARgamma agonist on ovarian tumors is not reported. In this study, we used two human ovarian carcinoma cell lines (ES-2 and PA-1) to examine the effects of the PPARgamma agonists troglitazone (TGZ) and ciglitazone (CGZ) on cell survival. CGZ and TGZ inhibited viability in a dose-dependent manner in both types of ovarian cancer cells. The agonists also decreased cellular proliferation in association with an increase in the number of cells arrested in the G0/G1 phase of the cell cycle. Moreover, they increased apoptosis while increasing caspase-3 activity. Incubation of both the cell lines with the PPARgamma agonists led to upregulated PPARgamma expression. This effect appeared to be PPARgamma independent because the PPARgamma antagonist GW9662 did not reverse it. Along with the induction of apoptosis in ovarian cancer cells, protein expression levels of p53 and Bax markedly increased in response to the PPARgamma agonists. Our results demonstrated that PPARgamma agonists inhibited the viability of human ovarian cancer cells, at least partly by inducing apoptosis. As a result, these agonists may serve as future drugs for the prevention and treatment of ovarian cancer.
Yang
Y-C
YC
Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan. eugene@ms2.mmh.org.tw
Tsao
Y-P
YP
Ho
T-C
TC
Choung
I-P
IP
D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D002839:Chromans; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D045162:Thiazolidinediones; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D000077288:Troglitazone; C039671:ciglitazone