[Effects of peroxisome proliferator-activated receptor-gamma agonist on Fas-mediated apoptosis in HT-29 cells].
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.
Chung
Yong Woo
YW
Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
Han
Dong Soo
DS
Kang
Eun Kyung
EK
Lee
Jin Sook
JS
Lee
Hang Rak
HR
Kim
Jin Bae
JB
Park
Jun Yong
JY
Kim
Yong Seok
YS
Lee
Oh Young
OY
Choi
Ho Soon
HS
Sohn
Joo Hyun
JH
Yoo
Dae Hyun
DH
Hahm
Joon Soo
JS
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*
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