Efficacy of menthol on cell viability of lung cancer cell line (A549): bioinformatics study and effect on the expression of the tumor suppressor gene p53.

Lung cancer is among the most common cancers in the world and is currently considered an epidemic on a global scale. Its rate is steadily increasing among men and women. The p53 gene is the most recognized tumor suppressor gene that is mutated in over 50% of human cancers. One of the methods to prevent cancer is the use of plant-based antioxidants. Menthol is a ten-carbon alcohol that is extracted from the pure essential oil of some plants, such as mint, oregano, and eucalyptus, and has food and medicinal uses. The present study aimed to investigate the effect of menthol on lung cancer cells, A549. In order to investigate the cytotoxicity of menthol on cancer cells and determine its half-maximal inhibitory concentration (IC50), the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test was performed. To investigate the effect of menthol on the expression of the p53 tumor suppressor gene, RNA extraction and cDNA synthesis were performed, and the change of gene expression in the concentration of IC50 was evaluated using the quantitative Real-Time PCR method. The binding of menthol to the P53 protein was investigated by the molecular docking method. According to the results of this research, the cytotoxic effect of menthol on the A549 cell line was proven, and the IC50 of menthol was determined at a concentration of 9.65 mg·mL− 1. Moreover, it was found that menthol upregulated p53 gene expression. The result of the bioinformatics analysis revealed that the amino acids asparagine and serine of the P53 mutant protein establish a hydrogen bond with menthol, resulting in the reduction of protein function and improved resistance against cancer. The interaction energy between menthol and P53 protein was determined to be -12.5 kJ·mol− 1. In conclusion, the menthol active ingredient increases the expression of the p53 tumor suppressor gene in lung cancer cell lines; therefore, it can be considered a possible alternative for lung cancer treatment after additional clinical studies.