Hypertonic environment elicits cyclooxygenase-2-driven prostaglandin E2 generation by colon cancer cells: role of cytosolic phospholipase A2-alpha and kinase signaling pathways.
Prostaglandins Leukot Essent Fatty Acids
; 82(2-3): 131-9, 2010.
Article
em En
| MEDLINE
| ID: mdl-20004562
Cyclooxygenase (COX)-2-derived prostaglandin (PG)E(2) controls many aspects of colon cancer development, modulating from apoptosis resistance and cell proliferation to angiogenesis, invasion, and metastasis. Here, we investigated the role of different phospholipases (PL)A(2) in supplying arachidonic acid (AA) for COX-2-dependent PGE(2) generation and signaling pathways involved in activation of colon cancer cells by a physiologically relevant stimulus. To emulate the hypertonic environment found physiologically in colon, the human colon cancer cell line Caco-2 was maintained in hypertonic complete DMEM medium. Human colon cancer cell line Caco-2 exposed to a hypertonic environment responded with marked AA release, COX-2 induction and PGE(2) generation. Selective secretory (s)PLA(2) and calcium-independent (i)PLA(2) inhibitors did not modify PGE(2) generation, while either COX-2 or cytosolic (c)PLA(2) inhibitors completely inhibited PGE(2) generation. cPLA(2)-alpha was responsible for AA supply for PGE(2) generation, but had no role in COX-2 induction. Mitogen-activated protein (MAP) kinases, ERK 1/2, p38, and JNK, participated in the signaling events that lead to PGE(2) generation by modulating AA release, but only ERK 1/2 was involved in COX-2 upregulation. Our results indicate that hypertonic stress activates PGE(2) generation by Caco-2 cells through a mechanism dependent on MAP kinase-regulated AA mobilization, increased cPLA(2)-alpha activity, and COX-2 induction.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dinoprostona
/
Ciclo-Oxigenase 2
/
Fosfolipases A2 do Grupo IV
/
Soluções Hipertônicas
Limite:
Humans
Idioma:
En
Revista:
Prostaglandins Leukot Essent Fatty Acids
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Reino Unido