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.
PPARgamma pathway activation results in apoptosis and COX-2 inhibition in HepG2 cells.
Ming-yi Li,Hua-yu Deng,Jia-ming Zhao,Dong Dai,Xiao-Yu Tan
Published 2003 in World Journal of Gastroenterology
ABSTRACT
PUBLICATION RECORD
- Publication year
2003
- Venue
World Journal of Gastroenterology
- Publication date
2003-06-15
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- apoptosis
A programmed cell-death phenotype measured in the treated HepG2 cells by staining and DNA fragmentation assays.
- bax and bak proteins
Pro-apoptotic Bcl-2 family proteins whose expression was measured in the treated HepG2 cells.
Aliases: Bax, Bak
- bcl-2
An anti-apoptotic protein whose abundance was examined in the treated HepG2 cells.
Aliases: B-cell lymphoma 2
- caspase-3
An executioner protease whose activity was assayed as part of the apoptosis mechanism analysis.
- cox-2
Cyclooxygenase-2, an enzyme whose mRNA and protein expression were measured in HepG2 cells.
Aliases: cyclooxygenase-2
- hepg2 cells
A human liver cancer cell line used as the experimental model in the assay.
Aliases: HepG2
- pge2
Prostaglandin E2, a lipid mediator whose level was monitored after troglitazone treatment.
Aliases: prostaglandin E2
- troglitazone
A PPAR gamma ligand used as the experimental treatment in HepG2 cells.
Aliases: TGZ, PPAR gamma ligand
REFERENCES
Showing 1-93 of 93 references · Page 1 of 1
CITED BY
Showing 1-71 of 71 citing papers · Page 1 of 1