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Modulating the ERK1/2–MMP1 Axis through Corosolic Acid Inhibits Metastasis of Human Oral Squamous Cell Carcinoma Cells

Corosolic acid (CA; 2α-hydroxyursolic acid) is a natural pentacyclic triterpenoid with antioxidant, antitumour and antimetastatic activities against various tumour cells during tumourigenesis. However, CA’s antitumour effect and functional roles on human oral squamous cell carcinoma (OSCC) cells are...

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Autores principales: Chen, Jen-Liang, Lai, Chung-Yu, Ying, Tsung-Ho, Lin, Chiao-Wen, Wang, Pei-Han, Yu, Fang-Jung, Liu, Chung-Jung, Hsieh, Yi-Hsien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395509/
https://www.ncbi.nlm.nih.gov/pubmed/34445346
http://dx.doi.org/10.3390/ijms22168641
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author Chen, Jen-Liang
Lai, Chung-Yu
Ying, Tsung-Ho
Lin, Chiao-Wen
Wang, Pei-Han
Yu, Fang-Jung
Liu, Chung-Jung
Hsieh, Yi-Hsien
author_facet Chen, Jen-Liang
Lai, Chung-Yu
Ying, Tsung-Ho
Lin, Chiao-Wen
Wang, Pei-Han
Yu, Fang-Jung
Liu, Chung-Jung
Hsieh, Yi-Hsien
author_sort Chen, Jen-Liang
collection PubMed
description Corosolic acid (CA; 2α-hydroxyursolic acid) is a natural pentacyclic triterpenoid with antioxidant, antitumour and antimetastatic activities against various tumour cells during tumourigenesis. However, CA’s antitumour effect and functional roles on human oral squamous cell carcinoma (OSCC) cells are utterly unknown. In this study, our results demonstrated that CA significantly exerted an inhibitory effect on matrix metalloproteinase (MMP)1 expression, cell migration and invasion without influencing cell growth or the cell cycle of human OSCC cells. The critical role of MMP1 was confirmed using the GEPIA database and showed that patients have a high expression of MMP1 and have a shorter overall survival rate, confirmed on the Kaplan–Meier curve assay. In the synergistic inhibitory analysis, CA and siMMP1 co-treatment showed a synergically inhibitory influence on MMP1 expression and invasion of human OSCC cells. The ERK1/2 pathway plays an essential role in mediating tumour progression. We found that CA significantly inhibits the phosphorylation of ERK1/2 dose-dependently. The ERK1/2 pathway played an essential role in the CA-mediated downregulation of MMP1 expression and in invasive motility in human OSCC cells. These findings first demonstrated the inhibitory effects of CA on OSCC cells’ progression through inhibition of the ERK1/2–MMP1 axis. Therefore, CA might represent a novel strategy for treating OSCC.
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spelling pubmed-83955092021-08-28 Modulating the ERK1/2–MMP1 Axis through Corosolic Acid Inhibits Metastasis of Human Oral Squamous Cell Carcinoma Cells Chen, Jen-Liang Lai, Chung-Yu Ying, Tsung-Ho Lin, Chiao-Wen Wang, Pei-Han Yu, Fang-Jung Liu, Chung-Jung Hsieh, Yi-Hsien Int J Mol Sci Article Corosolic acid (CA; 2α-hydroxyursolic acid) is a natural pentacyclic triterpenoid with antioxidant, antitumour and antimetastatic activities against various tumour cells during tumourigenesis. However, CA’s antitumour effect and functional roles on human oral squamous cell carcinoma (OSCC) cells are utterly unknown. In this study, our results demonstrated that CA significantly exerted an inhibitory effect on matrix metalloproteinase (MMP)1 expression, cell migration and invasion without influencing cell growth or the cell cycle of human OSCC cells. The critical role of MMP1 was confirmed using the GEPIA database and showed that patients have a high expression of MMP1 and have a shorter overall survival rate, confirmed on the Kaplan–Meier curve assay. In the synergistic inhibitory analysis, CA and siMMP1 co-treatment showed a synergically inhibitory influence on MMP1 expression and invasion of human OSCC cells. The ERK1/2 pathway plays an essential role in mediating tumour progression. We found that CA significantly inhibits the phosphorylation of ERK1/2 dose-dependently. The ERK1/2 pathway played an essential role in the CA-mediated downregulation of MMP1 expression and in invasive motility in human OSCC cells. These findings first demonstrated the inhibitory effects of CA on OSCC cells’ progression through inhibition of the ERK1/2–MMP1 axis. Therefore, CA might represent a novel strategy for treating OSCC. MDPI 2021-08-11 /pmc/articles/PMC8395509/ /pubmed/34445346 http://dx.doi.org/10.3390/ijms22168641 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Jen-Liang
Lai, Chung-Yu
Ying, Tsung-Ho
Lin, Chiao-Wen
Wang, Pei-Han
Yu, Fang-Jung
Liu, Chung-Jung
Hsieh, Yi-Hsien
Modulating the ERK1/2–MMP1 Axis through Corosolic Acid Inhibits Metastasis of Human Oral Squamous Cell Carcinoma Cells
title Modulating the ERK1/2–MMP1 Axis through Corosolic Acid Inhibits Metastasis of Human Oral Squamous Cell Carcinoma Cells
title_full Modulating the ERK1/2–MMP1 Axis through Corosolic Acid Inhibits Metastasis of Human Oral Squamous Cell Carcinoma Cells
title_fullStr Modulating the ERK1/2–MMP1 Axis through Corosolic Acid Inhibits Metastasis of Human Oral Squamous Cell Carcinoma Cells
title_full_unstemmed Modulating the ERK1/2–MMP1 Axis through Corosolic Acid Inhibits Metastasis of Human Oral Squamous Cell Carcinoma Cells
title_short Modulating the ERK1/2–MMP1 Axis through Corosolic Acid Inhibits Metastasis of Human Oral Squamous Cell Carcinoma Cells
title_sort modulating the erk1/2–mmp1 axis through corosolic acid inhibits metastasis of human oral squamous cell carcinoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395509/
https://www.ncbi.nlm.nih.gov/pubmed/34445346
http://dx.doi.org/10.3390/ijms22168641
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