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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF CANCER RESEARCH; v. 13, n. 4, p. 13-pg., 2023-01-01.

Resumo

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)

• Processo FAPESP: 19/06597-5 - Disrupção da resistência tumoral através de terapia direcionada a depleção de células tronco tumorais em Carcinomas Mucoepidermoides Salivares
• Beneficiário: Luan César da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/05710-4 - Disrupção da resistência tumoral através de terapia direcionada a depleção de células tronco tumorais em carcinomas espinocelulares de cabeça e pescoço
• Beneficiário: Pablo Agustin Vargas
• Modalidade de apoio: Auxílio à Pesquisa - Temático