title: Inhibition of ERK1/2 and CREB phosphorylation by caspase-dependent mechanism enhances apoptosis in a fibrosarcoma cell line treated with butyrate.
abstract: 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.
authors.affiliation: 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.
authors.forename: Flávia L A
authors.initials: FL
authors.lastname: Rabelo
authors.forename: Catherine
authors.initials: C
authors.lastname: Ropert
authors.forename: Mariana G
authors.initials: MG
authors.lastname: Ramos
authors.forename: Cláudio A
authors.initials: CA
authors.lastname: Bonjardim
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Gazzinelli
authors.forename: Jacqueline I
authors.initials: JI
authors.lastname: Alvarez-Leite
mesh_terms: 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
chemical_list: 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