Ming-Yi Li1, Hua Deng, Jia-Ming Zhao, Dong Dai, Xiao-Yu Tan. 1. Department of General Surgery,Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong Province, China. zjmyli@sohu.com
Abstract
AIM: To investigate whether troglitazone (TGZ), the peroxisome proliferator-activated receptor (PPAR) gamma ligand, can induce apoptosis and inhibit cell proliferation in human liver cancer cell line HepG2 and to explore the molecular mechanisms. METHODS: (3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), ((3)H) Thymidine incorporation, Hochest33258 staining, DNA ladder, enzyme-linked immunosorbent assay (ELISA), RT-PCR, Northern and Western blotting analyses were employed to investigate the effect of TGZ on HepG2 cells and related molecular mechanisms. RESULTS: TGZ was found to inhibit the growth of HepG2 cells and to induce apoptosis. During the process, the expression of COX-2 mRNA and protein and Bcl-2 protein was down-regulated, while that of Bax and Bak proteins was up-regulated, and the activity of caspase-3 was elevated. Furthermore, the level of PGE(2) was decreased transiently after 12 h of treatment with 30 microM troglitazone. CONCLUSION: TGZ inhibits cell proliferation and induces apoptosis in HepG2 cells, which may be associated with the activation of caspase-3-like proteases, down-regulation of the expression of COX-2 mRNA and protein, Bcl-2 protein, the elevation of PGE2 levels, and up-regulation of the expressions of Bax and Bak proteins.
AIM: To investigate whether troglitazone (TGZ), the peroxisome proliferator-activated receptor (PPAR) gamma ligand, can induce apoptosis and inhibit cell proliferation in humanliver cancer cell line HepG2 and to explore the molecular mechanisms. METHODS: (3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), ((3)H) Thymidine incorporation, Hochest33258 staining, DNA ladder, enzyme-linked immunosorbent assay (ELISA), RT-PCR, Northern and Western blotting analyses were employed to investigate the effect of TGZ on HepG2 cells and related molecular mechanisms. RESULTS:TGZ was found to inhibit the growth of HepG2 cells and to induce apoptosis. During the process, the expression of COX-2 mRNA and protein and Bcl-2 protein was down-regulated, while that of Bax and Bak proteins was up-regulated, and the activity of caspase-3 was elevated. Furthermore, the level of PGE(2) was decreased transiently after 12 h of treatment with 30 microM troglitazone. CONCLUSION:TGZ inhibits cell proliferation and induces apoptosis in HepG2 cells, which may be associated with the activation of caspase-3-like proteases, down-regulation of the expression of COX-2 mRNA and protein, Bcl-2 protein, the elevation of PGE2 levels, and up-regulation of the expressions of Bax and Bak proteins.
Authors: G D Demetri; C D Fletcher; E Mueller; P Sarraf; R Naujoks; N Campbell; B M Spiegelman; S Singer Journal: Proc Natl Acad Sci U S A Date: 1999-03-30 Impact factor: 11.205
Authors: Priyadarshini Raman; Barbara L F Kaplan; Jerry T Thompson; John P Vanden Heuvel; Norbert E Kaminski Journal: Mol Pharmacol Date: 2011-04-21 Impact factor: 4.436
Authors: Ann K Y To; George G Chen; Ursula P F Chan; Caiguo Ye; Jing P Yun; Rocky L K Ho; Art Tessier; Juanita L Merchant; Paul B S Lai Journal: Biochim Biophys Acta Date: 2010-09-17