title: Troglitazone induced apoptosis via PPARγ activated POX-induced ROS formation in HT29 cells.
abstract: OBJECTIVE
  In order to investigate the potential mechanisms in troglitazone-induced apoptosis in HT29 cells, the effects of PPARγ and POX-induced ROS were explored.
  
  
  METHODS
  [3- (4, 5)-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, Annexin V and PI staining using FACS, plasmid transfection, ROS formation detected by DCFH staining, RNA interference, RT-PCR & RT-QPCR, and Western blotting analyses were employed to investigate the apoptotic effect of troglitazone and the potential role of PPARγ pathway and POX-induced ROS formation in HT29 cells.
  
  
  RESULTS
  Troglitazone was found to inhibit the growth of HT29 cells by induction of apoptosis. During this process, mitochondria related pathways including ROS formation, POX expression and cytochrome c release increased, which were inhibited by pretreatment with GW9662, a specific antagonist of PPARγ. These results illustrated that POX upregulation and ROS formation in apoptosis induced by troglitazone was modulated in PPARγ-dependent pattern. Furthermore, the inhibition of ROS and apoptosis after POX siRNA used in troglitazone-treated HT29 cells indicated that POX be essential in the ROS formation and PPARγ-dependent apoptosis induced by troglitazone.
  
  
  CONCLUSIONS
  The findings from this study showed that troglitazone-induced apoptosis was mediated by POX-induced ROS formation, at least partly, via PPARγ activation.
authors: Chinese Academy of Sciences, Beijing, China. avaecn@gmail.com
authors: Jing
authors: J
authors: Wang
authors: XiaoWen
authors: X
authors: Lv
authors: JiePing
authors: J
authors: Shi
authors: XiaoSong
authors: X
authors: Hu
authors: YuGuo
authors: Y
authors: DU
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology*; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D047495:PPAR gamma / Q000378:metabolism*; D011394:Proline Oxidase / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
chemical_list: D000970:Antineoplastic Agents; D002839:Chromans; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D045304:Cytochromes c; D011394:Proline Oxidase; D000077288:Troglitazone