Dexamethasone suppresses apoptosis in a human gastric cancer cell line through modulation of bcl-x gene expression.
Treatment of human gastric cancer TMK-1 cells with transcription and translation inhibitors rapidly triggered cell apoptosis. Along with cell apoptosis, the Bcl-xS level was markedly upregulated suggesting a crucial role of this protein in promoting the apoptotic process. In the presence of dexamethasone, however, cell apoptosis was greatly attenuated as demonstrated by DNA histogram shift and DNA fragmentation. Studies using the glucocorticoid receptor antagonist RU486 indicated that attenuation of apoptosis was mediated through glucocorticoid receptors. Dexamethasone not only suppressed the apoptosis-associated upregulation of Bcl-xS but also enhanced the basal level of Bcl-xL in the cells. In addition, bcl-x mRNA stability was significantly extended in the presence of dexamethasone. These results indicate that dexamethasone exerted a protective effect and delayed apoptosis of TMK-1 cells by modulating bcl-x gene expression.
Chang
T C
TC
Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, ROC.
Hung
M W
MW
Jiang
S Y
SY
Chu
J T
JT
Chu
L L
LL
Tsai
L C
LC
D017209:Apoptosis / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D015735:Mifepristone / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D013274:Stomach Neoplasms; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D051020:bcl-X Protein; D003609:Dactinomycin; D015735:Mifepristone; D004004:Dichlororibofuranosylbenzimidazole; D003907:Dexamethasone; D003513:Cycloheximide