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

Author(s)

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

• Document type: Journal article
• Source: ARCHIVES OF ORAL BIOLOGY; v. 135, p. 9-pg., 2022-03-01.

Abstract

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)

• FAPESP's process: 16/07129-7 - Comparison of the effects of different pharmacological fatty acid synthase (FASN) inhibitors on the cell cycle and apoptosis associated with morphological alterations in human oral Squamous carcinoma cells (SCC-9)
• Grantee: Isadora Ferrari Teixeira
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 16/24906-7 - Effects of pharmacological inhibition of the TE, KS and ER domains of fatty acid synthase (FASN)enzyme on the processes of adhesion, migration and invasion of oral squamous cell carcinoma cells (SCC-9)
• Grantee: Willian Peter Boelcke
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 14/20832-3 - The association of Orlistat with chemotherapic agents for the treatment of oral squamous cell carcinoma: an in vitro and in vivo study in orthotopic models
• Grantee: Edgard Graner
• Support Opportunities: Regular Research Grants