COMBINATION OF HDAC AND NF-KB INHIBITORS DEPLET CANCER STEM CELL POPULATION AND SENSITIZE HNSCC TO CHEMOTHERAPY

Abstract

<h3>Objectives</h3> Recent evidence suggests a major role for cancer stem cell (CSC) as responsible for tumor progression, recurrence, and chemotherapy and radiotherapy resistance in head and neck squamous cell carcinoma (HNSCC). Epigenetic modifications and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation have been associated with CSC behavior and represent promising targets for HNSCC treatment. The aim was to explore the potential of the histone deacetylase (HDAC) and NF-kB inhibitors (SAHA and emetine, respectively) as potential modulators of the CSC population in HNSCC. <h3>Study Design</h3> SAHA and emetine cytotoxic concentration were determined using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) cell viability assay for the SCC-4 and SCC9 HNSCC cell lines. The CSC population was estimated by aldehyde dehydrogenases activity using flow cytometry, tumosphere formation, and clonogenic assay. The drugs were tested isolated and in combination. <h3>Results</h3> Treatment with SAHA and emetine isolated decreased the CSC in SCC-4 and SCC-9 population in all assays. The combination of both drugs led to a more significant reduction in CSC population and sensitivity to chemotherapy with cisplatin. <h3>Conclusions</h3> Our findings suggests that the inhibition of HDAC activity combined with the depletion of NF-kB pathway effectively depleted CSC population and that the double inhibition can be a possible target for new adjuvant therapies in HNSCC.