Pharmacological fatty acid synthase inhibitors differently affect the malignant phenotype of oral cancer cells.

Autor(es)

Boelcke, Willian Peter ; Teixeira, Isadora Ferrari ; Aquino, Iara Gonalves ; Mazzaro, Amanda Ramos ; Cuadra-Zelaya, Florence Juana Maria ; de Souza, Ana Paula ; Salo, Tuula ; Della Coletta, Ricardo ; Graner, Edgard ; Bastos, Debora Campanella

• Tipo de documento: Artigo Científico
• Fonte: ARCHIVES OF ORAL BIOLOGY; v. 135, p. 9-pg., 2022-03-01.

Resumo

Objective: Fatty acid synthase levels are associated with aggressiveness, prognosis, and risk of metastasis in oral squamous cell carcinomas. This enzyme contains seven catalytic domains and its inhibition by synthetic or natural drugs has antineoplastic properties such as C75, which is a synthetic inhibitor of the beta-ketoacyl synthase domain, the antibiotic triclosan, ligand of the enoyl reductase domain, and the antiobesity drug orlistat, which inhibits the thioesterase domain. Here, we sought to investigate and compare the in vitro effects of C75, triclosan, and orlistat on malignant phenotypes of the cell line SCC-9: proliferation, cell cycle, apoptosis, adhesion, migration, and invasion.& nbsp;Design: Half-maximal inhibitory concentration (IC50) was determined using cell viability assays. Cell death and cell cycle progression were analyzed by Annexin V-PE/7-ADD-PerCP labeling and propidium iodide staining, respectively. Cell migration and invasion were assayed by transwells assays and cell adhesion using collagen and fibronectin.& nbsp;Results: C75 showed the lowest IC50 and higher inhibition of lipid droplets at low concentrations and reduced cell motility. Triclosan showed the intermediate IC50 value, excellent reduction of lipid bodies at the IC50 when compared with C75 and orlistat. Also, triclosan reduced cell cycle progression, adhesion, migration, and invasion of SCC-9 and induced the highest levels of apoptosis. Orlistat promoted cell cycle arrest, but showed the lowest induction of apoptosis and did not affected invasion and adhesion of SCC-9.& nbsp;Conclusion: Altogether, despite the particular effects of the analyzed fatty acid synthase inhibitors, triclosan showed to better interfere in tumorigenic phenotypes of SCC-9 cells. (AU)

• Processo FAPESP: 16/07129-7 - Avaliação dos efeitos de diferentes inibidores farmacológicos da enzima ácido graxo sintase (FASN) sobre o ciclo celular e apoptose associados a alterações morfológicas de células de Carcinoma espinocelular oral humano (SCC-9)
• Beneficiário: Isadora Ferrari Teixeira
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 16/24906-7 - Comparação dos efeitos da inibição farmacológica dos domínios TE, KS e ER da enzima ácido graxo sintase (FASN) sobre os processos de adesão, migração e invasão de células de carcinoma espinocelular oral (SCC-9)
• Beneficiário: Willian Peter Boelcke
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 14/20832-3 - Efeitos da associação de Orlistat com agentes quimioterápicos em carcinoma espinocelular de língua: estudo in vitro e em modelos ortotópicos
• Beneficiário: Edgard Graner
• Modalidade de apoio: Auxílio à Pesquisa - Regular