Repurposing NFκB and HDAC inhibitors to individually target cancer stem cells and non-cancer stem cells from mucoepidermoid carcinomas

• Published in: American journal of cancer research 2023-01, Vol.13 (4), p.1547-1559
• Main Authors: Silva, Luan César, Borgato, Gabriell Bonifácio, Wagner, Vivian Petersen, Martins, Manoela Domingues, Lopes, Márcio Ajudarte, Santos-Silva, Alan Roger, De Castro, Gilberto, Kowalski, Luiz Paulo, Squarize, Cristiane Helena, Vargas, Pablo Agustin, Castilho, Rogerio Moraes
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 2156-6976; 2156-6976

Drug resistance remains a major obstacle in the treatment of mucoepidermoid carcinomas (MEC) leading 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 population 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 concentrations 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.