title: [Effects of peroxisome proliferator-activated receptor-gamma agonist on Fas-mediated apoptosis in HT-29 cells].
abstract: OBJECTIVE
  Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) plays a critical role in adipocytes differentiation and insulin sensitivity and is also related to regulation of inflammation and cell proliferation. The aim of this study was to investigate the PPAR-gamma agonist-induced apoptosis and effects of PPAR-gamma agonist on Fas-mediated apoptosis in a human colon cancer cell line.
  
  
  METHODS
  Cell survival and apoptosis of HT-29 cells were measured by trypan blue exclusion method and FACScan after treatment with 15d-PGJ2, ciglitazone and IgM anti-Fas antibody (CH11), respectively or simultaneously. Also, activation of caspase-3 and caspase-8 was analyzed to assess the effects of PPAR-gamma and Fas on apoptosis signaling pathways.
  
  
  RESULTS
  CH11 induced apoptosis of HT-29 cells. 15d-PGJ2 or ciglitazone alone did not induce apoptosis, but combined stimulation with CH11 synergistically induced apoptosis. Also, 15d-PGJ2 alone did not activate caspase-3, but CH11 and 15d-PGJ2 synergistically activated caspase-3. CH11 activated procaspase-8, but 15d-PGJ2 did not.
  
  
  CONCLUSIONS
  PPAR-gamma was not an enough condition to induce apoptosis of HT-29 cells. Apoptosis was induced by high dose Fas, and was enhanced with PPAR-gamma agonist. PPAR-gamma agonist seems to enhance Fas-mediated apoptosis by affecting the way between caspase-8 and caspase-3. Further research is needed to use PPAR-gamma agonists as chemopreventive and therapeutic agent for colon cancer and to find the pathways of PPAR-gamma on apoptotic cascade of colon cancer cells.
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Chung
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Han
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kang
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Lee
authors.forename: Hang Rak
authors.initials: HR
authors.lastname: Lee
authors.forename: Jin Bae
authors.initials: JB
authors.lastname: Kim
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Kim
authors.forename: Oh Young
authors.initials: OY
authors.lastname: Lee
authors.forename: Ho Soon
authors.initials: HS
authors.lastname: Choi
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Sohn
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Yoo
authors.forename: Joon Soo
authors.initials: JS
authors.lastname: Hahm
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D047188:Chalcones; D004789:Enzyme Activation / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000502:physiology; D045162:Thiazolidinediones / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists* / Q000502:physiology; D019014:fas Receptor / Q000276:immunology / Q000494:pharmacology*
chemical_list: C477819:15-deoxyprostaglandin J2; C418965:4-dimethylamino-3',4'-dimethoxychalcone; D047188:Chalcones; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D019014:fas Receptor; D002599:Chalcone; D020169:Caspases; D015230:Prostaglandin D2; C039671:ciglitazone