TUMORIGENIC EFFECT MEDIATED BY FATTY ACID SYNTHASE IN A MURINE MAMMARY ADENOCARCINOMA MODELS FED WITH HIGH PALMITIC ACID AND FRUCTOSE DIET

TAMARA MAZO; VICTORIA FERRERO; NERI NELSO BAROTTO; JULIETA DON; LAURA YENNERICH; ERICA SOLLA; LILIANA SOSA; VALERIA RODRÍGUEZ; AMADO QUINTAR; MARIA EUGENIA PASQUALINI

Mar de Plata

Congreso; ANNUAL MEETING OF BIOSCIENCE SOCIETIES 2022; 2022

Sociedad argentina de investigación clinica

Breast cancer (BC) is the first leading cause of mortality in womenand is associated with genetic and epigenetic factors such as dietarycompounds. The fatty acid synthase (FASN) is involved in de novolipogenesis, catalyzing the synthesis of endogenous fatty acids. Inearly stages of carcinogenesis, the activation of FASN is mediatedby hypoxia, which is induced by high concentrations of simple carbohydratesand fats. Its overexpression is associated with a poor prognosis,however, the dietary regulation of FASN in BC development isstill unknown. The aim of this study was to evaluate the variation indietary palmitic acid (PA) and fructose (Fr) on the regulation of FASNexpression mediated by hypoxia in murine BC development. BALB/cmice (n=40) were divided in 4 dietary groups, CONTROL (6%cornoil+30%Fr), PCS (20%palm oil+15%Fr), PBA (20%corn oil+45%Fr)and PCS+PBA (20% palm oil+45%Fr). After 90 days mice were inoculatedwith murine breast adenocarcinoma LM3 cells (1x106cell).In this model we evaluated tumor volume (calimeter), lipid profile(gas chromatography, GC), FASN expression (Western Blot and immunohistochemistry)and tumor histology (H/E). In vitro model: culturedLM3 were treated with PA (40μM-50μM) and/or Fr (2.5μM) for24hs. We evaluated viability (resazurin), apoptosis (Hoechst), lipidprofile (GC), FASN expression. Three replicates were minimally performedby experiment and analyzed by ANOVA. The PCS presentedthe highest percentage of PA and the PBA, a high percentage of ω-6PUFAs in membranes respect to the other groups. The PCS+PBAdiet produced an increment in tumor growth, infiltration and necrosis.FASN expression was increased in this group as well as afterPA and Fr (40/2.5uM) LM3 treatment (p<0.05).The PA and Fr(40/2.5uM) decreased LM3 apoptotic cells and PA 40μM increasedcell viability (p<0.05). We demonstrated that diets high in PA and Frinduce tumor development in murine BC, mediated by an incrementin FASN enzyme expression.