Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most fatal malignancies worldwide and
despite using various therapeutic strategies for the treatment of HNSCC, the surveillance rate is low. Telomerase has been remarked
as the primary targets in cancer therapy. Considering the key regulatory role of epigenetic mechanisms in controlling genome
expression, the present study aimed to investigate the effects of two epigenetic modulators, a DNA methylation inhibitor and a
histone deacetylase inhibitor on cell migration, proliferation, hTERT gene expression, and telomerase activity in HNSCC cell lines.
Methods: Human HNSCC cell lines were treated with Azacitidine and Trichostatin A to investigate their effects on telomerase
gene expression and activity. Cell viability, migration, hTERT gene expression, and telomerase activity were studied using MTT
colorimetric assay, scratch wound assay, qRT-PCR, and TRAP assay, respectively.
Results: Azacitidine at concentrations of ≤1μM and Trichostatin A at 0.1 to 0.3nM concentrations significantly decreased FaDu
and Cal-27 cells migration. The results showed that Azacitidine significantly decreased hTERT gene expression and telomerase
activity in FaDu and Cal-27 cell lines. However, there were no significant changes in hTERT gene expression at different
concentrations of Trichostatin A in both cell lines. Trichostatin A treatment affected telomerase activity at the high dose of 0.3 nM
Conclusion: The findings revealed that unlike histone deacetylase inhibitor, Azacitidine as an inhibitor of DNA methylation
decreases telomerase expression in HNSCC cells. This might suggest the potential role of DNA methyltransferase inhibitors in
telomerase-based therapeutic approaches in squamous cell carcinoma.