Hypertonic environment elicits cyclooxygenase-2-driven prostaglandin E2 generation by colon cancer cells: Role of cytosolic phospholipase A2-α and kinase signaling pathways

Gentile, Luciana B.; Piva, Bruno; Capizzani, Bianca C.; Furlaneto, Luiz G.B.; Moreira, Luciana S.; Zamith-Miranda, Daniel; Diaz, Bruno L.

doi:10.1016/j.plefa.2009.11.005

« Previous Next »Prostaglandins, Leukotrienes and Essential Fatty Acids
Volume 82, Issue 2 , Pages 131-139, February 2010

Hypertonic environment elicits cyclooxygenase-2-driven prostaglandin E₂ generation by colon cancer cells: Role of cytosolic phospholipase A₂-α and kinase signaling pathways☆

Luciana B. Gentile
- Divisão de Biologia Celular, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, RJ 20231-050, Brazil
- Programa de Pós-Graduação em Ciências Morfológicas, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil
Bruno Piva
- Laboratório de Inflamação, Programa de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Bloco C, room C1-024, Rio de Janeiro, RJ, CEP 21941-902, Brazil
Bianca C. Capizzani
- Laboratório de Inflamação, Programa de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Bloco C, room C1-024, Rio de Janeiro, RJ, CEP 21941-902, Brazil
Luiz G.B. Furlaneto
- Divisão de Biologia Celular, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, RJ 20231-050, Brazil
Luciana S. Moreira
- Divisão de Biologia Celular, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, RJ 20231-050, Brazil
Daniel Zamith-Miranda
- Laboratório de Inflamação, Programa de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Bloco C, room C1-024, Rio de Janeiro, RJ, CEP 21941-902, Brazil
Bruno L. Diaz
- Laboratório de Inflamação, Programa de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Bloco C, room C1-024, Rio de Janeiro, RJ, CEP 21941-902, Brazil
- Corresponding author. Tel.: +552125626509; fax: +552122808193.

Received 5 December 2008; received in revised form 11 November 2009; accepted 12 November 2009. published online 10 December 2009.

Abstract

Cyclooxygenase (COX)-2-derived prostaglandin (PG)E₂ 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)A₂ in supplying arachidonic acid (AA) for COX-2-dependent PGE₂ 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 PGE₂ generation. Selective secretory (s)PLA₂ and calcium-independent (i)PLA₂ inhibitors did not modify PGE₂ generation, while either COX-2 or cytosolic (c)PLA₂ inhibitors completely inhibited PGE₂ generation. cPLA₂-α was responsible for AA supply for PGE₂ 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 PGE₂ generation by modulating AA release, but only ERK 1/2 was involved in COX-2 upregulation. Our results indicate that hypertonic stress activates PGE₂ generation by Caco-2 cells through a mechanism dependent on MAP kinase-regulated AA mobilization, increased cPLA₂-α activity, and COX-2 induction.