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

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 ß- 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. 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. 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. 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.

Anticancer properties of the fatty acid synthase inhibitor TVB-3166 on oral squamous cell carcinoma cell lines.

OBJECTIVE: Fatty acid synthase (FASN) is overexpressed in several human cancers, including oral squamous cell carcinoma (OSCC). TVB-3166 is a recently described FASN inhibitor with antitumor effects and potential clinical relevance. The objective of this study was to evaluate the effects of TVB-3166 on OSCC cell lines. MATERIALS AND METHODS: The OSCC cell line SCC-9 modified to express ZsGreen (ZsG) (SCC-9 ZsG) and its in vivo selected metastatic derivative LN-1A were used to evaluate anticancer properties of TVB-3166. Cell viability was determined using MTT assays and proliferation determined by cell counting in a Neubauer chamber. Cell death and cell cycle progression were analyzed by Annexin V-PE/7-ADD-PerCP labeling and PI staining, respectively. Cell migration was assayed by scratch assays and cell adhesion using myogel. Production of FASN, p-AKT, CPT1-α, and epithelial-mesenchymal transition (EMT) markers were examined by Western blotting. RESULTS: TVB-3166 significantly reduced cell viability and proliferation, promoted cell cycle arrest and apoptosis, and increased adhesion to myogel in both OSCC cell lines. Finally, the drug reduced SCC-9 ZsG migration. CONCLUSION: Our results demonstrated that TVB-3166 has anticancer effects on both SCC-9 ZsG and its metastatic version LN-1A, which are worthy of investigation in preclinical models for OSCC.