Korean J Gastroenterol.  2003 Jul;42(1):35-41.

Effects of Peroxisome Proliferator-activated Receptor-gamma Agonist on Fas-mediated Apoptosis in HT-29 Cells

• Chung YW
• Han DS
• Kang EK
• Lee JS
• Lee HR
• Kim JB
• Park JY
• Kim YS
• Lee OY
• Choi HS
• Sohn JH
• Yoo DH
• Hahm JS

Abstract

BACKGROUND/AIMS: 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.

Keyword

Apoptosis; PPAR-gamma; Fas; Caspases; Colon neoplasms

MeSH Terms

Antigens, CD95/immunology/*pharmacology
Apoptosis/*drug effects
Caspases/metabolism
Cell Survival/drug effects
Cells, Cultured
Chalcone/*analogs & derivatives/pharmacology
Chalcones
Enzyme Activation/drug effects
HT29 Cells
Humans
Prostaglandin D2/*analogs & derivatives/pharmacology
Receptors, Cytoplasmic and Nuclear/*agonists/physiology
Thiazolidinediones/pharmacology
Transcription Factors/*agonists/physiology