Eugenol Inhibits the Biological Activities of an Oral Squamous Cell Carcinoma Cell Line SCC9 via Targeting MIF

Anticancer Agents Med Chem. 2022 Aug 4;22(15):2799-2806. doi: 10.2174/1871520622666220324105435.

Abstract

Background: Oral squamous cell carcinoma (OSCC) is a rampant cancer type in head and neck cancers with a poor prognosis and a high recurrence rate. Eugenol shows an anticancer effect in a variety of cancers, but it has been rarely studied in oral squamous cell carcinoma (OSCC).

Objective: The purpose of this study was to explore the role of Eugenol in OSCC and the underlying mechanism.

Methods: After different concentrations of Eugenol (0, 200, 400, and 800 μM) treatment, the viability, proliferation, migration, and invasion of OSCC cell line SCC9 were measured by CCK-8, colony formation, wound-healing, and transwell assays, respectively. TUNEL staining was employed to detect apoptosis. Western blotting was used to evaluate gene expression at the protein level. Molecular docking was used to identify the target of Eugenol.

Results: Eugenol decreased the proliferation and reduced the abilities of invasion and migration along with the expression of matrix metalloproteinases (MMP) 2 and MMP9 in SCC9 cells. On the contrary, the ratio of apoptotic cells was increased by Eugenol. In addition, Eugenol down-regulated B cell lymphoma-2 (Bcl-2) expression, but up-regulated BCL-2 associated X (Bax), cleaved caspase 3, and cleaved poly-ADP ribose polymerase (PARP) expression. Meanwhile, Eugenol exerted its effect on SCC9 cells in a concentration-dependent manner. Eugenol could bind to macrophage migration inhibitory factor (MIF), the expression of which was down-regulated after Eugenol treatment. Besides, overexpression of MIF reversed all the effects of Eugenol on OSCC cells.

Conclusion: In summary, Eugenol suppressed the malignant processes of OSCC cells by targeting MIF, which could guide the clinical application of Eugenol in OSCC.

Keywords: Oral squamous cell carcinoma; TUNEL staining; eugenol; invasion; macrophage migration inhibitory factor; migration.

MeSH terms

  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Eugenol / pharmacology
  • Eugenol / therapeutic use
  • Head and Neck Neoplasms*
  • Humans
  • Intramolecular Oxidoreductases / pharmacology
  • Intramolecular Oxidoreductases / therapeutic use
  • Macrophage Migration-Inhibitory Factors* / pharmacology
  • Macrophage Migration-Inhibitory Factors* / therapeutic use
  • Molecular Docking Simulation
  • Mouth Neoplasms* / drug therapy
  • Mouth Neoplasms* / metabolism
  • Proto-Oncogene Proteins c-bcl-2
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • Macrophage Migration-Inhibitory Factors
  • Proto-Oncogene Proteins c-bcl-2
  • Eugenol
  • Intramolecular Oxidoreductases
  • MIF protein, human