Ubiquitination of p53 is involved in troglitazone induced apoptosis in cervical cancer cells.
Peroxisome proliferator-activated receptor gamma (PPAR-γ), a ligand-dependent nuclear transcription factor, has been found to widely exist in tumor tissues and plays an important role in affecting tumor cell growth. In this study, we investigated the effect of PPAR-γ on aspects of the cervical cancer malignant phenotype, such as cell proliferation and apoptosis. Cell growth assay, Western blotting, Annexin V and flow cytometry analysis consistently showed that treatment with troglitazone (TGZ, a PPAR-γ agonist) led to dose-dependent inhibition of cervical cancer cell growth through apoptosis, whereas T0070907 (another PPAR-γ antagonist???) had no effect on Hela cell proliferation and apoptosis. Furthermore, we also detected the protein expression of p53, p21 and Mdm2 to explain the underlying mechanism of PPAR-γ on cellular apoptosis. Our work, finally, demonstrated the existence of the TGZ-PPAR-γ-p53 signaling pathway to be a critical regulator of cell apoptosis. These results suggested that PPAR-γ may be a potential therapeutic target for cervical cancer.
Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, China E-mail : dspei@xzmc.edu.cn; jnzheng@xzmc.edu.cn.
Hui-Min
HM
Chen
Ding-Guo
DG
Zhang
Jin-Xia
JX
Wu
Dong-Sheng
DS
Pei
Jun-Nian
JN
Zheng
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002839:Chromans / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D047495:PPAR gamma / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D054875:Ubiquitination / Q000187:drug effects* / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics*
D002839:Chromans; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047495:PPAR gamma; D045162:Thiazolidinediones; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D000077288:Troglitazone