Repurposing NF kappa B and HDAC inhibitors to individually target cancer stem cells and non-cancer stem cells from mucoepidermoid carcinomas

Author(s)

Silva, Luan Cesar ; Borgato, Gabriell Bonifacio ; Wagner, Vivian Petersen ; Martins, Manoela Domingues ; Santos-Silva, Alan Roger ; de Castro Jr, Gilberto ; Kowalski, Luiz Paulo ; Squarize, Cristiane Helena ; Vargas, Pablo Agustin ; Castilho, Rogerio Moraes

• Document type: Journal article
• Source: AMERICAN JOURNAL OF CANCER RESEARCH; v. 13, n. 4, p. 13-pg., 2023-01-01.

Abstract

Drug resistance remains a major obstacle in the treatment of mucoepidermoid carcinomas (MEC) lead-ing to tumor recurrence, disease progression, and metastasis. Emerging evidence suggests that drug resistance is mediated by the presence of a highly adaptative subpopulation of cancer cells known as cancer stem cells (CSC). We have previously reported that solid tumors use NFkB signaling as a chemotherapy-resistant mechanism. We have also shown that interfering with the epigenome of solid tumors is an effective strategy to control the popula-tion of CSC. Here, we sought to investigate the effects of the NFkB inhibitor emetine and the HDAC inhibitor SAHA on the biology of MEC CSC and assessed whether this combination therapy would favor the standard of care therapy comprised of the administration of Cisplatin (CDDP). Our findings suggested that the administration of low concen-trations of emetine and SAHA is more effective in disrupting CSC in MEC, while the administration of emetine in combination with CDDP constitutes an effective therapy to target non-CSC MEC tumor cells. (AU)

• FAPESP's process: 19/06597-5 - Disrupting tumor resistance through therapy targeting depletion of cancer stem cells in Salivary Mucoepidermoid Carcinomas
• Grantee: Luan César da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/05710-4 - Disrupting tumor resistance through therapy targeting depletion of cancer stem cells in head and neck cancer
• Grantee: Pablo Agustin Vargas
• Support Opportunities: Research Projects - Thematic Grants