Tumorigenic effect mediated by fatty acid synthase in a murine mammary adenocarcinoma model fed with high palmitic acid and fructose diet
Date
2022Author
Mazo, Tamara Magali
Ferrero, Victoria
Barotto, Nelso Neri
Don, Julieta
Yennerich, Laura Irene
Solla, Erika
Sosa, Liliana del Valle
Rodríguez, V.
Quintar, Amado Alfredo
Pasqualini, María Eugenia
Metadata
Show full item recordAbstract
Breast cancer (BC) is the first leading cause of mortality in women
and is associated with genetic and epigenetic factors such as dietary
compounds. The fatty acid synthase (FASN) is involved in de novo
lipogenesis, catalyzing the synthesis of endogenous fatty acids. In
early stages of carcinogenesis, the activation of FASN is mediated
by hypoxia, which is induced by high concentrations of simple carbohydrates and fats. Its overexpression is associated with a poor prognosis, however, the dietary regulation of FASN in BC development is
still unknown. The aim of this study was to evaluate the variation in
dietary palmitic acid (PA) and fructose (Fr) on the regulation of FASN
expression mediated by hypoxia in murine BC development. BALB/c
mice (n=40) were divided in 4 dietary groups, CONTROL (6%corn
oil+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 inoculated with 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: cultured LM3 were treated with PA (40μM-50μM) and/or Fr (2.5μM) for
24hs. We evaluated viability (resazurin), apoptosis (Hoechst), lipid
profile (GC), FASN expression. Three replicates were minimally performed by experiment and analyzed by ANOVA. The PCS presented
the highest percentage of PA and the PBA, a high percentage of ω-6
PUFAs in membranes respect to the other groups. The PCS+PBA
diet produced an increment in tumor growth, infiltration and necrosis. FASN expression was increased in this group as well as after PA and Fr (40/2.5uM) LM3 treatment (p<0.05). The PA and Fr
(40/2.5uM) decreased LM3 apoptotic cells and PA 40μM increased
cell viability (p<0.05). We demonstrated that diets high in PA and Fr
induce tumor development in murine BC, mediated by an increment
in FASN enzyme expression.