HDAC AND NFKB INHIBITORS REDUCE CANCER STEM CELLS AND SENSITIZE MUCOEPIDERMOID CARCINOMA CELL LINES TO CISPLATIN

• Published in: Oral surgery, oral medicine, oral pathology and oral radiology oral medicine, oral pathology and oral radiology, 2022-09, Vol.134 (3), p.e205-e205
• Main Authors: Da Silva, Luan César, Borgato, Gabriel Bonifácio, Wagner, Vivian Petersen, Martins, Manoela Domingues, Squarize, Cristiane Helena, Castilho, Rogerio Moraes, Vargas, Pablo Agustin
• Format: Article
• Language: English
• ISSN: 2212-4403; 2212-4411
• DOI: 10.1016/j.oooo.2022.01.634

To evaluate the potential of histone deacetylase (HDAC) suberoylanilide hydroxamic acid (SAHA) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) (emetine) inhibitors, isolated and associated with cisplatin (CDDP) in salivary gland mucoepidermoid carcinoma (MEC) cell lines, specifically through cancer stem cell (CSC) modulation. Cell viability was determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Immunofluorescence staining was performed to identify the acetylation of lysine 9 from histone H3 protein (H3k9ac) and phosphorylated protein p65 (NFkB pathway). CSC was evaluated by quantifying the enzymatic activity of aldehyde dehydrogenases (ALDH) using flow cytometry and by in vitro tumorsphere formation. A single administration of SAHA (1 μM) induced histone acetylation, whereas 0.05 μM of emetine resulted in inhibition of the NF-kB pathway. We showed a disruption of CSC, illustrated by a reduction of enzymatic activity of ALDH and inhibition of tumorsphere formation. Furthermore, we observed that MEC tumor cells were sensitized to CDDP after the administration of a combination of SAHA and emetine. Our findings suggest that HDAC and NF-kB inhibitors might be an alternative approach to treat MEC through disruption of CSC and sensitizing cells to conventional therapy.