trichostatin-a and Squamous-Cell-Carcinoma-of-Head-and-Neck

Topics: Apoptosis; Cell Line; Head and Neck Neoplasms; Humans; Hydroxamic Acids; Squamous Cell Carcinoma of Head and Neck

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.. 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.. 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.. 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.

Topics: Antineoplastic Agents; Apoptosis; Azacitidine; Cell Line, Tumor; Cell Survival; DNA Methylation; DNA Modification Methylases; Drug Development; Enzyme Activation; Enzyme Inhibitors; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Histone Deacetylase Inhibitors; Histones; Humans; Hydroxamic Acids; Peptide Fragments; Signal Transduction; Squamous Cell Carcinoma of Head and Neck; Telomerase

Topics: Cell Line, Tumor; Cell Proliferation; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Histone Chaperones; Histones; Humans; Hydroxamic Acids; Ki-67 Antigen; Methylation; MicroRNAs; Mouth Neoplasms; Retinoblastoma Protein; Squamous Cell Carcinoma of Head and Neck

Recent progression in the understanding of stem cell biology has greatly facilitated the identification and characterization of cancer stem cells (CSCs). Moreover, evidence has accumulated indicating that conventional cancer treatments are potentially ineffective against CSCs. Histone deacetylase inhibitors (HDACi) have multiple biologic effects consequent to alterations in the patterns of acetylation of histones and are a promising new group of anticancer agents. In this study, we investigated the effects of two HDACi, suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), on two CD44+ cancer stem-like cell lines from squamous cell carcinoma of the head and neck (SCCHN) cultured in serum-free medium containing epidermal growth factor and basic fibroblast growth factor. Histone deacetylase inhibitors inhibited the growth of SCCHN cell lines in a dose-dependent manner as measured by MTS assays. Moreover, HDACi induced cell cycle arrest and apoptosis in these SCCHN cell lines. Interestingly, the expression of cancer stem cell markers, CD44 and ABCG2, on SCCHN cell lines was decreased by HDACi treatment. In addition, HDACi decreased mRNA expression levels of stemness-related genes and suppressed the epithelial-mesencymal transition phenotype of CSCs. As expected, the combination of HDACi and chemotherapeutic agents, including cisplatin and docetaxel, had a synergistic effect on SCCHN cell lines. Taken together, our data indicate that HDACi not only inhibit the growth of SCCHN cell lines by inducing apoptosis and cell cycle arrest, but also alter the cancer stem cell phenotype in SCCHN, raising the possibility that HDACi may have therapeutic potential for cancer stem cells of SCCHN.

Topics: Antineoplastic Agents; Apoptosis; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Carcinoma, Squamous Cell; Cell Cycle Checkpoints; Cell Line, Tumor; Drug Resistance, Neoplasm; Drug Synergism; Epithelial-Mesenchymal Transition; Head and Neck Neoplasms; Histone Deacetylase Inhibitors; Humans; Hyaluronan Receptors; Hydroxamic Acids; Neoplasm Proteins; Neoplastic Stem Cells; Phenotype; Squamous Cell Carcinoma of Head and Neck