Tumor development in breast cancer by activation of fatty acid synthase in palmitic acid and fructose-rich diets

FERRERO V; MAZO TM; BAROTTO N; DON J; SOSA L; RODRÍGUEZ V; QUINTAR A; PASQUALINI ME

Córdoba

Jornada; XXIII Jornada de Investigación Científica; 2022

FCM-UNC

Breast cancer is the leading cause of mortality in women and is associated not only with genetic but also with epigenetic factors, such as dietary factors. In our laboratory we demonstrated that dietary polyunsaturated lipids (PUFAs) activate enzymes such as cyclooxygenases, lipooxygenases and other peroxidases involved in the regulation of carcinogenesis. Fatty acid synthase (FASN) is involved in de novo lipogenesis, catalyzing the synthesis of endogenous fatty acids. In early stages of carcinogenesis, FASN activation is mediated by hypoxia, induced by high concentrations of sugars and fats. Its overexpression is associated with a poor prognosis. However, the dietary regulation of FASN in breast cancer development is still unknown. The objective was to evaluate whether variation in dietary palmitic acid (PA) and fructose (Fr) regulates hypoxia-mediated FASN expression in murine breast cancer development. An in vivo model was used: BALB/c mice (n=40) divided into dietary groups, CONTROL (6%corn oil+30%fructose), PCS (20%palm oil+15%fructose), PBA (20%corn oil+45%fructose) and PCS+PBA (20%palm oil+45%fructose), which were inoculated at 90 days with murine breast adenocarcinoma LM3 cells (1x106cell). Tumor volume (calimeter), lipid profile (gas chromatography: GC), FASN expression (western blot and immunohistochemistry) and histology (H/E) were evaluated. In vitro: LM3 cells were treated with AP (40µM-50µM) and/or Fr (2.5µM) for 24hs. Viability (resazurin), apoptosis (Hoechst), lipid profile (GC), FASN expression (Western Blot) were evaluated. Experiments were repeated minimally three times and analyzed by ANOVA. The PCS+PBA diet produced an increase in growth, infiltration, tumor necrosis and FASN expression (p