Cargando…

Cholic Acid Stimulates MMP-9 in Human Colon Cancer Cells via Activation of MAPK, AP-1, and NF-κB Activity

Matrix metalloproteinase-9 (MMP-9) plays a crucial role in cell invasion and cancer metastasis. In this study, we showed that cholic acid (CA), a major primary bile acid, can induce MMP-9 expression in colon cancer HT29 and SW620 cells. CA increased reactive oxygen species (ROS) production and also...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Shinan, Ung, Trong Thuan, Nguyen, Thi Thinh, Sah, Dhiraj Kumar, Park, Seon Young, Jung, Young Do
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279292/
https://www.ncbi.nlm.nih.gov/pubmed/32408577
http://dx.doi.org/10.3390/ijms21103420
_version_ 1783543525956124672
author Li, Shinan
Ung, Trong Thuan
Nguyen, Thi Thinh
Sah, Dhiraj Kumar
Park, Seon Young
Jung, Young Do
author_facet Li, Shinan
Ung, Trong Thuan
Nguyen, Thi Thinh
Sah, Dhiraj Kumar
Park, Seon Young
Jung, Young Do
author_sort Li, Shinan
collection PubMed
description Matrix metalloproteinase-9 (MMP-9) plays a crucial role in cell invasion and cancer metastasis. In this study, we showed that cholic acid (CA), a major primary bile acid, can induce MMP-9 expression in colon cancer HT29 and SW620 cells. CA increased reactive oxygen species (ROS) production and also activated phosphorylation of ERK1/2, JNK, and p38 MAPK. Specific inhibitors and mutagenesis studies showed that ERK1/2 and JNK functioned as upstream signals in the activation of AP-1, and p38 MAPK functioned as an upstream signal in the activation of NF-κB. N-acetyl-L-cysteine (NAC, an ROS scavenger) and diphenyleneiodonium chloride (DPI, an NADPH oxidase inhibitor) inhibited CA-induced activation of ERK1/2, JNK, and p38 MAPK, indicating that ROS production by NADPH oxidase could be the furthest upstream signal in MMP-9 expression. Colon cancer cells pretreated with CA showed remarkably enhanced invasiveness. Such enhancement was partially abrogated by MMP-9-neutralizing antibodies. These results demonstrate that CA could induce MMP-9 expression via ROS-dependent ERK1/2, JNK-activated AP-1, and p38-MAPK-activated NF-κB signaling pathways, which in turn stimulate cell invasion in human colon cancer cells.
format Online
Article
Text
id pubmed-7279292
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72792922020-06-15 Cholic Acid Stimulates MMP-9 in Human Colon Cancer Cells via Activation of MAPK, AP-1, and NF-κB Activity Li, Shinan Ung, Trong Thuan Nguyen, Thi Thinh Sah, Dhiraj Kumar Park, Seon Young Jung, Young Do Int J Mol Sci Article Matrix metalloproteinase-9 (MMP-9) plays a crucial role in cell invasion and cancer metastasis. In this study, we showed that cholic acid (CA), a major primary bile acid, can induce MMP-9 expression in colon cancer HT29 and SW620 cells. CA increased reactive oxygen species (ROS) production and also activated phosphorylation of ERK1/2, JNK, and p38 MAPK. Specific inhibitors and mutagenesis studies showed that ERK1/2 and JNK functioned as upstream signals in the activation of AP-1, and p38 MAPK functioned as an upstream signal in the activation of NF-κB. N-acetyl-L-cysteine (NAC, an ROS scavenger) and diphenyleneiodonium chloride (DPI, an NADPH oxidase inhibitor) inhibited CA-induced activation of ERK1/2, JNK, and p38 MAPK, indicating that ROS production by NADPH oxidase could be the furthest upstream signal in MMP-9 expression. Colon cancer cells pretreated with CA showed remarkably enhanced invasiveness. Such enhancement was partially abrogated by MMP-9-neutralizing antibodies. These results demonstrate that CA could induce MMP-9 expression via ROS-dependent ERK1/2, JNK-activated AP-1, and p38-MAPK-activated NF-κB signaling pathways, which in turn stimulate cell invasion in human colon cancer cells. MDPI 2020-05-12 /pmc/articles/PMC7279292/ /pubmed/32408577 http://dx.doi.org/10.3390/ijms21103420 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Shinan
Ung, Trong Thuan
Nguyen, Thi Thinh
Sah, Dhiraj Kumar
Park, Seon Young
Jung, Young Do
Cholic Acid Stimulates MMP-9 in Human Colon Cancer Cells via Activation of MAPK, AP-1, and NF-κB Activity
title Cholic Acid Stimulates MMP-9 in Human Colon Cancer Cells via Activation of MAPK, AP-1, and NF-κB Activity
title_full Cholic Acid Stimulates MMP-9 in Human Colon Cancer Cells via Activation of MAPK, AP-1, and NF-κB Activity
title_fullStr Cholic Acid Stimulates MMP-9 in Human Colon Cancer Cells via Activation of MAPK, AP-1, and NF-κB Activity
title_full_unstemmed Cholic Acid Stimulates MMP-9 in Human Colon Cancer Cells via Activation of MAPK, AP-1, and NF-κB Activity
title_short Cholic Acid Stimulates MMP-9 in Human Colon Cancer Cells via Activation of MAPK, AP-1, and NF-κB Activity
title_sort cholic acid stimulates mmp-9 in human colon cancer cells via activation of mapk, ap-1, and nf-κb activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279292/
https://www.ncbi.nlm.nih.gov/pubmed/32408577
http://dx.doi.org/10.3390/ijms21103420
work_keys_str_mv AT lishinan cholicacidstimulatesmmp9inhumancoloncancercellsviaactivationofmapkap1andnfkbactivity
AT ungtrongthuan cholicacidstimulatesmmp9inhumancoloncancercellsviaactivationofmapkap1andnfkbactivity
AT nguyenthithinh cholicacidstimulatesmmp9inhumancoloncancercellsviaactivationofmapkap1andnfkbactivity
AT sahdhirajkumar cholicacidstimulatesmmp9inhumancoloncancercellsviaactivationofmapkap1andnfkbactivity
AT parkseonyoung cholicacidstimulatesmmp9inhumancoloncancercellsviaactivationofmapkap1andnfkbactivity
AT jungyoungdo cholicacidstimulatesmmp9inhumancoloncancercellsviaactivationofmapkap1andnfkbactivity