Title:Effects of Kojic Acid-mediated Sonodynamic Therapy as a Matrix
Metalloprotease-9 Inhibitor against Oral Squamous Cell Carcinoma: A
Bioinformatics Screening and In Vitro Analysis
Volume: 21
Issue: 4
Author(s): Maryam Pourhajibagher*, Mojgan Alaeddini, Shahroo Etemad-Moghadam, Steven Parker and Abbas Bahador*
Affiliation:
- Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Department of Microbiology,
School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Fellowship in Clinical Laboratory Sciences,
BioHealth Lab, Tehran, Iran
Keywords:
Oral squamous cell carcinoma, Kojic acid, matrix metalloprotease, sonodynamic therapy, bioinformatics, mucous membrane.
Abstract:
Background: Oral squamous cell carcinoma (OSCC) is a type of cancer that is responsible
for a significant amount of morbidity and mortality worldwide. Researchers are searching for promising
therapeutic methods to manage this cancer. In this study, an in silico approach was used to
evaluate the activity of sonodynamic therapy (SDT) based on the use of Kojic acid as a sonosensitizer
to inhibit matrix metalloprotease-9 (MMP-9) in OSCC.
Materials and Methods: The three-dimensional structure of MMP-9 was predicted and validated by
computational approaches. The possible functional role of MMP-9 was determined in terms of Gene
Ontology (GO) enrichment analysis. In silico, molecular docking was then performed to evaluate the
binding energies of Kojic acid with MMP-9, and ADME parameters and toxicity risks were predicted.
The pharmacokinetics and drug-likeness properties of Kojic acid were assessed. Moreover, after the
determination of the cytotoxicity effect of Kojic acid-mediated SDT, the change of mmp-9 gene expression
was assessed on OSCC cells.
Results: The results of the study showed that Kojic acid could efficiently interact with MMP-9 protein
with a strong binding affinity. Kojic acid obeyed Lipinski’s rule of five without violation and
exhibited drug-likeness. The cytotoxic effects of Kojic acid and ultrasound waves on the OSCC cells
were dose-dependent, and the lowest expression level of the mmp-9 gene was observed in SDT.
Conclusions: Overall, Kojic acid-mediated SDT as an MMP-9 inhibitor can be a promising adjuvant
treatment for OSCC. The study highlights the potential of In silico approaches to evaluate therapeutic
methods for cancer treatment.
