Back to Search
Start Over
Differential apoptosis by indomethacin in gastric epithelial cells through the constitutive expression of wild-type p53 and/or up-regulation of c-myc
- Source :
- Biochemical Pharmacology. 58:193-200
- Publication Year :
- 1999
- Publisher :
- Elsevier BV, 1999.
-
Abstract
- Nonsteroidal anti-inflammatory drug (NSAID)-induced apoptosis is considered to be an important mechanism in the antineoplastic effects and damage produced by the drugs in the gastrointestinal tract. In this study, two different gastric cancer cell lines, MKN28 (mutant-type p53) and AGS (wild-type p53), were compared as to growth inhibition, apoptosis, and cell cycle and apoptosis-related gene expression in response to indomethacin treatment. Cell growth was measured by MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Apoptosis was characterized by acridine orange staining and DNA fragmentation, and cell cycle kinetics by flow cytometry. The mRNA and protein levels of p53, p21waf1/cip1, and c-myc were determined by Northern and Western blotting. The results showed that indomethacin initiated growth inhibition and apoptosis in both cell lines without cell cycle shifting. AGS cells were more sensitive to growth inhibitory activity and apoptosis of indomethacin than MKN28 cells. In MKN28 cells, the levels of p53, p21waf1/cip1, and c-myc mRNA remained unchanged over the 24-hr treatment with indomethacin, but the p53 protein level was elevated after 4 hr. There was no change in the p21waf1/cip1 and c-myc protein levels in the MKN28 cells. In AGS cells, a progressive increase in c-myc mRNA and protein levels was noted, while p53 and p21waf1/cip1 remained unchanged. It can be concluded that wild-type p53 and/or up-regulation of c-myc is associated with indomethacin-mediated differential apoptosis in gastric epithelial cells.
- Subjects :
- Cyclin-Dependent Kinase Inhibitor p21
Indomethacin
Genes, myc
Gene Expression
Apoptosis
Biology
Biochemistry
Flow cytometry
chemistry.chemical_compound
Cyclins
Tumor Cells, Cultured
medicine
Humans
RNA, Messenger
Pharmacology
medicine.diagnostic_test
Cell growth
Anti-Inflammatory Agents, Non-Steroidal
Cell Cycle
Stomach
Epithelial Cells
Cell cycle
Up-Regulation
chemistry
Cell culture
Cell Cycle Kinetics
Cancer research
DNA fragmentation
Tumor Suppressor Protein p53
Growth inhibition
Cell Division
Subjects
Details
- ISSN :
- 00062952
- Volume :
- 58
- Database :
- OpenAIRE
- Journal :
- Biochemical Pharmacology
- Accession number :
- edsair.doi.dedup.....096e7acc52e287c76c1407485fc8b582