Breast adenocarcinoma tumorigenesis promotion by overexpression of FASN and HIF1-α induced by palmitic acid and fructose
Cancer cells are characterized by high cell proliferation within the participation of FASN (fatty acid synthase), catalyzed enzime of fatty acids synthesis, mainly palmitic acid (PA) (1,2). The activation of FASN gene is mediated by alpha subunit hypoxia-inducible factor 1 (HIF1-α)...
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| Autores principales: | , , , , , , , |
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| Formato: | Artículo revista |
| Lenguaje: | Español |
| Publicado: |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2023
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| Materias: | |
| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/42679 |
| Aporte de: |
| Sumario: | Cancer cells are characterized by high cell proliferation within the participation of FASN (fatty acid synthase), catalyzed enzime of fatty acids synthesis, mainly palmitic acid (PA) (1,2). The activation of FASN gene is mediated by alpha subunit hypoxia-inducible factor 1 (HIF1-α), increasing the glycolysis in breast cancer (3). We propose to evaluate whether dietary variation in PA and fructose (Fr) regulates FASN and HIF1-α expression in murine breast cancer development.
BALB/c mice were divided into 4 dietary groups (n=20c/u), 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). Animals were inoculated at 90 days with murine breast adenocarcinoma cells (LM3: 1x106 cells). At 120 days we evaluated: host biochemical parameters, tumor volume, metastasis and necrosis (H/E), lipid profile (GC), FASN and HIF1-α tumor expression (Western Blot:WB, qPCR, IHQ). In vitro: LM3 cells were treated with PA 40uM and Fr 2.5mM. We analyzed viability, cell proliferation (Resazurin and Hoechst), FASN expression (WB) and lipid profile (GC). At least three replicates were performed per experiment and analyzed by ANOVA(p<0.05).
The animals fed with PCS+PBA presented the higher tumor volume, infiltration and necrosis (p<0.05). The PCS group presented the highest percentage of PA and the PBA group, the highest percentage of ω-6 PUFAs in tumor tissue (p<0.05).The PCS+PBA diet produced an increment in FASN (IQH-WB) and HIF1-α (IHQ) expression (p<0.05). Fructose rich diet (PBA) induced an increment of FASN mRNA in tumor tissue (qPCR) (p<0.05). PA40µM and Fr2.5mM treatment decreased apoptosis and increased cell viability relative to control in LM3 cells(p<0.05). The combination of PA and Fr (40µM/2.5mM) induced an increment in FASN expression (WB) (p<0.05).
Palmitic acid and fructose high diets induced FASN and HIF1-α overexpression, promoting cell proliferation in murine breast cancer. |
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