DEPLETION OF MUCOEPIDERMOID CARCINOMA CANCER STEM CELLS BY HISTONE DEACETYLASE AND NFkB INHIBITORS

Abstract

Background Platinum-based systemic therapy is used in metastatic or disseminated mucoepidermoid carcinoma (MEC), yet it presented low response rates. Further, drug resistance remains a major obstacle to MEC treatment leading to tumor recurrence, disease progression, and metastasis, which could be associated with cancer stem cells (CSCs). Objective Investigate the effects of SAHA (Histone deacetylase inhibitor) and Emetine (NFkB inhibitor) on CSCs derived from three MEC cell lines. Study Design UM-HMC-1, UM-HMC-2, and UM-HMC-3A MEC cell lines were used to investigate the effects of SAHA and Emetine on CSCs. The concentration of the drugs was obtained by a previous proliferation assay. CSCs were assayed by in vitro tumorspheres formation in two moments. Results First, we demonstrated that a single administration of SAHA and Emetine was able to inhibit the tumorsphere formation in all MEC cell lines. Next, we evaluated whether the therapy was able to reduce the number of formed tumorspheres, and we showed a complete reduction in UM-HMC2 (** p<0.01) by Emetine, and a significant reduction in UM-HMC3a (* p<0.05) by SAHA. Conclusion Our findings suggest that HDAC and NFKB inhibitors might be an alternative approach to treating MEC, although they disrupt CSC. Funding Fapesp 2016/05710-4 Platinum-based systemic therapy is used in metastatic or disseminated mucoepidermoid carcinoma (MEC), yet it presented low response rates. Further, drug resistance remains a major obstacle to MEC treatment leading to tumor recurrence, disease progression, and metastasis, which could be associated with cancer stem cells (CSCs). Investigate the effects of SAHA (Histone deacetylase inhibitor) and Emetine (NFkB inhibitor) on CSCs derived from three MEC cell lines. UM-HMC-1, UM-HMC-2, and UM-HMC-3A MEC cell lines were used to investigate the effects of SAHA and Emetine on CSCs. The concentration of the drugs was obtained by a previous proliferation assay. CSCs were assayed by in vitro tumorspheres formation in two moments. First, we demonstrated that a single administration of SAHA and Emetine was able to inhibit the tumorsphere formation in all MEC cell lines. Next, we evaluated whether the therapy was able to reduce the number of formed tumorspheres, and we showed a complete reduction in UM-HMC2 (** p<0.01) by Emetine, and a significant reduction in UM-HMC3a (* p<0.05) by SAHA. Our findings suggest that HDAC and NFKB inhibitors might be an alternative approach to treating MEC, although they disrupt CSC.