351. [Effects of peroxisome proliferator-activated receptor-gamma agonist on Fas-mediated apoptosis in HT-29 cells].
- Author
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Chung YW, Han DS, Kang EK, Lee JS, Lee HR, Kim JB, Park JY, Kim YS, Lee OY, Choi HS, Sohn JH, Yoo DH, and Hahm JS
- Subjects
- Caspases metabolism, Cell Survival drug effects, Cells, Cultured, Chalcone pharmacology, Chalcones, Enzyme Activation drug effects, HT29 Cells, Humans, Prostaglandin D2 pharmacology, Receptors, Cytoplasmic and Nuclear physiology, Thiazolidinediones pharmacology, Transcription Factors physiology, fas Receptor immunology, Apoptosis drug effects, Chalcone analogs & derivatives, Prostaglandin D2 analogs & derivatives, Receptors, Cytoplasmic and Nuclear agonists, Transcription Factors agonists, fas Receptor pharmacology
- 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.
- Published
- 2003