Inhibition of ERK1/2 and CREB phosphorylation by caspase-dependent mechanism enhances apoptosis in a fibrosarcoma cell line treated with butyrate.
We evaluated the role of MAPKs on apoptosis induced by butyrate in cells derived from a human fibrosarcoma (2C4). Culture of 2C4 cells in 5% of fetal bovine serum (FBS) induced ERK1/2 and CREB phosphorylation and delayed apoptosis induced by butyrate. Butyrate inhibited phosphorylation of ERK1/2 and CREB. Furthermore, the use of specific inhibitors PD98059 (MEK) and H89 (PKA), which block ERK1/2 and CREB phosphorylation, accelerated butyrate induced cell death in 2C4 cells. The butyrate effect was shown to be dependent on caspase activation, once caspase inhibitors restored phosphorylation of ERK1/2 and CREB in 2C4 cells. However, the proteolytic effect of caspases was not directly on ERK1/2 and CREB proteins. In conclusion, butyrate induced apoptosis in 2C4 cells is regulated by the levels of ERK1/2 and CREB phosphorylation in a caspase dependent mechanism.
Rabelo
Flávia L A
FL
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Caixa Postal 486, CEP 30 161-970, Belo Horizonte, Minas Gerais, Brazil.
Ropert
Catherine
C
Ramos
Mariana G
MG
Bonjardim
Cláudio A
CA
Gazzinelli
Ricardo T
RT
Alvarez-Leite
Jacqueline I
JI
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D002087:Butyrates / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005354:Fibrosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002087:Butyrates; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007546:Isoquinolines; D013449:Sulfonamides; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one