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

doi:10.1016/j.plefa.2009.11.005

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

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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.

Original language	English (US)
Pages (from-to)	131-139
Number of pages	9
Journal	Prostaglandins Leukotrienes and Essential Fatty Acids
Volume	82
Issue number	2-3
DOIs	https://doi.org/10.1016/j.plefa.2009.11.005
State	Published - Feb 2010
Externally published	Yes

Keywords

COX-2
CPLA-α
Colon Cancer
Hypertonic stress
MAP kinase
PGE

ASJC Scopus subject areas

Clinical Biochemistry
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.plefa.2009.11.005

Cite this

Gentile, L. B., Piva, B., Capizzani, B. C., Furlaneto, L. G. B., Moreira, L. S., Zamith-Miranda, D., & Diaz, B. L. (2010). Hypertonic environment elicits cyclooxygenase-2-driven prostaglandin E₂ generation by colon cancer cells: Role of cytosolic phospholipase A₂-α and kinase signaling pathways. Prostaglandins Leukotrienes and Essential Fatty Acids, 82(2-3), 131-139. https://doi.org/10.1016/j.plefa.2009.11.005

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. et al.
In: Prostaglandins Leukotrienes and Essential Fatty Acids, Vol. 82, No. 2-3, 02.2010, p. 131-139.

Research output: Contribution to journal › Article › peer-review

Gentile, LB, Piva, B, Capizzani, BC, Furlaneto, LGB, Moreira, LS, Zamith-Miranda, D & Diaz, BL 2010, 'Hypertonic environment elicits cyclooxygenase-2-driven prostaglandin E₂ generation by colon cancer cells: Role of cytosolic phospholipase A₂-α and kinase signaling pathways', Prostaglandins Leukotrienes and Essential Fatty Acids, vol. 82, no. 2-3, pp. 131-139. https://doi.org/10.1016/j.plefa.2009.11.005

Gentile LB, Piva B, Capizzani BC, Furlaneto LGB, Moreira LS, Zamith-Miranda D et al. Hypertonic environment elicits cyclooxygenase-2-driven prostaglandin E₂ generation by colon cancer cells: Role of cytosolic phospholipase A₂-α and kinase signaling pathways. Prostaglandins Leukotrienes and Essential Fatty Acids. 2010 Feb;82(2-3):131-139. doi: 10.1016/j.plefa.2009.11.005

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

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.",

keywords = "COX-2, CPLA-α, Colon Cancer, Hypertonic stress, MAP kinase, PGE",

author = "Gentile, {Luciana B.} and Bruno Piva and Capizzani, {Bianca C.} and Furlaneto, {Luiz G.B.} and Moreira, {Luciana S.} and Daniel Zamith-Miranda and Diaz, {Bruno L.}",

note = "Funding Information: This work was supported by grants from Conselho Nacional de Desenvolvimento Cient{\'i}fico e Tecnol{\'o}gico (CNPq, Brazil) and Funda{\c c}{\~a}o Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ, Brazil) (to B.L. Diaz) and a Ministry of Health (Brazil) PhD fellowship (to L.B. Gentile). Authors wish to thank Dr. Christianne Bandeira-Melo and Karen A. Bell for their comments on the manuscript. ",

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AU - Capizzani, Bianca C.

AU - Furlaneto, Luiz G.B.

AU - Moreira, Luciana S.

AU - Zamith-Miranda, Daniel

AU - Diaz, Bruno L.

N1 - Funding Information: This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) and Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ, Brazil) (to B.L. Diaz) and a Ministry of Health (Brazil) PhD fellowship (to L.B. Gentile). Authors wish to thank Dr. Christianne Bandeira-Melo and Karen A. Bell for their comments on the manuscript.

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N2 - 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.

AB - 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.

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