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 target 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 Trichostatin A.
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.