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)

• Grant number: 16/07129-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2016
• Effective date (End): December 31, 2017
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Débora Campanella Bastos
• Grantee: Isadora Ferrari Teixeira
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Fatty acid synthase (FASN) enzyme is responsible for the endogenous synthesis of long chain fatty acids from acetyl-CoA and malonyl-CoA. Structurally, FASN has two polypeptide chains with seven different domains in each. In contrast with normal tissues, FASN is overexpressed in several types of epithelial malignancies and associated with worse prognosis in most of these tumors, including oral squamous cell carcinoma (SCC). Due to differential expression between normal and neoplastic tissues, FASN has emerged as promising therapeutic target for cancer. Several FASN inhibitors have been shown to demonstrate antiproliferative and antineoplastic properties. Cerulenin (CER) and its analogue, C75, reacts with the KS domain of FASN. The antibiotic triclosan (TCS) interacts with the ER domain. Also, the antiobesity drug orlistat (ORL) was also demonstrate to inhibit the TE domain of FASN. Previous studies from our group have shown that treatment with ORL reduces the volume of orthotopic SCC tumors and promoted cell cycle arrest and apoptosis in SCC oral (SCC-9). Moreover, the pharmacological inhibition of different domains of FASN can modulate different metabolic pathways in both normal and tumor prostate cells. The goal of this study is to compare the effects of different pharmacological FASN inhibitors focusing on the cell cycle and apoptosis and correlate with morphological alterations in SCC-9 cells.