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

• Published in: International journal of molecular sciences 2021-08, Vol.22 (16), p.8641
• Main Authors: Chen, Jen-Liang, Lai, Chung-Yu, Ying, Tsung-Ho, Lin, Chiao-Wen, Wang, Pei-Han, Yu, Fang-Jung, Liu, Chung-Jung, Hsieh, Yi-Hsien
• Format: Article
• Language: English
• Subjects: Acids; Antioxidants; Apoptosis; Cancer therapies; Cell adhesion & migration; Cell cycle; Cell growth; corosolic acid; ERK1/2; Extracellular signal-regulated kinase; Flow cytometry; human oral squamous cell carcinoma cells; Invasiveness; Liver cancer; Matrix metalloproteinase; Matrix metalloproteinases; Metalloproteinase; Metastases; Metastasis; MMP1; Motility; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; Phosphorylation; Phytochemicals; Proteins; Squamous cell carcinoma; Tongue; Tumorigenesis; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22168641

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.