Administration of 4‑hexylresorcinol increases p53‑mediated transcriptional activity in oral cancer cells with the p53 mutation.

The p53 mutation is inherent in over 50% of human cancers. In head and neck squamous cell carcinoma, the p53 mutation is associated with a poor prognosis. 4‑Hexylresorcinol (4HR) is a pharmacologic chaperone. The present study aimed to investigate the effect of 4HR on p53 transcriptional activity in oral carcinoma cells with p53 mutations. To identify conformational changes induced by 4HR administration, peptides including the DNA‑binding domain from mutant and wild‑type p53 were synthesized, and Fourier transform infrared spectroscopy was performed. To determine the effect of 4HR on p53 mutant carcinoma cells, western blot analysis, p53 transcriptional activity analysis, MTT assay and apoptosis immunocytochemistry were performed. The YD‑15 cell line has a mutation in the DNA binding domain of p53 (Glu258Ala). When p53 Ala‑258 was coupled by 4HR, the p53 Ala‑258 structure lost its original conformation and approached a conformation similar to that of p53 Glu‑258. In the cell experiments, 4HR administration to p53 mutant cells increased p53 transcriptional activity and the expression levels of apoptosis‑associated proteins such as B‑cell lymphoma 2 (BCL2), BCL2‑associated X (BAX) and BCL2‑associated agonist of cell death (BAD). Accordingly, 4HR administration on YD‑15 cells decreased cell viability and increased apoptosis. In conclusion, 4HR is a potential substance for use in the recovery of loss‑of‑function in mutant p53 as a pharmacologic chaperone.