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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Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2023
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/42679 |
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I10-R327-article-42679 |
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Universidad Nacional de Córdoba |
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I-10 |
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R-327 |
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Revista de la Facultad de Ciencias Médicas de Córdoba |
| language |
Español |
| format |
Artículo revista |
| topic |
palmitic acid fructose Breast cancer fatty acid synthase (FASN) HIF1-α ácido palmítico fructosa Cáncer de mama ácido graso sintasa (FASN) HIF1-α |
| spellingShingle |
palmitic acid fructose Breast cancer fatty acid synthase (FASN) HIF1-α ácido palmítico fructosa Cáncer de mama ácido graso sintasa (FASN) HIF1-α Ferrero, V Mazo , T Barotto, NN Don, JA Granton , F Moreira-Espinoza, MJ Rodríguez , V Pasqualini , ME Breast adenocarcinoma tumorigenesis promotion by overexpression of FASN and HIF1-α induced by palmitic acid and fructose |
| topic_facet |
palmitic acid fructose Breast cancer fatty acid synthase (FASN) HIF1-α ácido palmítico fructosa Cáncer de mama ácido graso sintasa (FASN) HIF1-α |
| author |
Ferrero, V Mazo , T Barotto, NN Don, JA Granton , F Moreira-Espinoza, MJ Rodríguez , V Pasqualini , ME |
| author_facet |
Ferrero, V Mazo , T Barotto, NN Don, JA Granton , F Moreira-Espinoza, MJ Rodríguez , V Pasqualini , ME |
| author_sort |
Ferrero, V |
| title |
Breast adenocarcinoma tumorigenesis promotion by overexpression of FASN and HIF1-α induced by palmitic acid and fructose |
| title_short |
Breast adenocarcinoma tumorigenesis promotion by overexpression of FASN and HIF1-α induced by palmitic acid and fructose |
| title_full |
Breast adenocarcinoma tumorigenesis promotion by overexpression of FASN and HIF1-α induced by palmitic acid and fructose |
| title_fullStr |
Breast adenocarcinoma tumorigenesis promotion by overexpression of FASN and HIF1-α induced by palmitic acid and fructose |
| title_full_unstemmed |
Breast adenocarcinoma tumorigenesis promotion by overexpression of FASN and HIF1-α induced by palmitic acid and fructose |
| title_sort |
breast adenocarcinoma tumorigenesis promotion by overexpression of fasn and hif1-α induced by palmitic acid and fructose |
| description |
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. |
| publisher |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2023 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/42679 |
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I10-R327-article-426792023-10-19T21:20:01Z Breast adenocarcinoma tumorigenesis promotion by overexpression of FASN and HIF1-α induced by palmitic acid and fructose Promoción de la tumorigénesis en adenocarcinoma de mama por sobreexpresión de FASN y HIF1-α inducida por ácido palmítico y fructosa Ferrero, V Mazo , T Barotto, NN Don, JA Granton , F Moreira-Espinoza, MJ Rodríguez , V Pasqualini , ME palmitic acid fructose Breast cancer fatty acid synthase (FASN) HIF1-α ácido palmítico fructosa Cáncer de mama ácido graso sintasa (FASN) HIF1-α 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. Las células cancerosas se caracterizan por una alta proliferación celular en la cual participa la FASN (fatty acid synthase), catalizando la síntesis de ácidos grasos principalmente del ácido palmítico(AP) (1,2). La activación del gen FASN es mediada por la subunidad alfa del factor 1 inducible por hipoxia (HIF1-α), aumentando la glucólisis en el cáncer de mama (3). Proponemos evaluar si la variación dietaria de AP y fructosa (Fr) regula la expresión de FASN y de HIF1-α en el desarrollo de cáncer de mama murino. Ratones BALB/c fueron divididos en grupos dietarios (n=20c/u), CONTROL (6%aceite de maíz+30%Fr), PCS (20% aceite de palma+15%Fr), PBA (20% aceite de maíz+45%Fr) y PCS+PBA (20% aceite de palma+45%Fr) e inoculados a los 90 días con células de adenocarcinoma de mama murino (LM3: 1x106cél). A los 120 días evaluamos: parámetros bioquímicos, volumen tumoral, metástasis y necrosis (H/E), perfil lipídico (GC), expresión de FASN y HIF1-α tumoral (Western Blot:WB, qPCR, IHQ). In vitro: LM3 fueron tratadas con AP40uM y Fr2,5mM. Analizamos viabilidad, proliferación celular (Resazurina y Hoechst), expresión de FASN (WB) y perfil lipídico (GC). Los experimentos se repitieron mínimamente tres veces y se analizaron por ANOVA(p<0,05). Los animales alimentados con PCS+PBA presentaron un aumento en el crecimiento, infiltración y necrosis tumoral (p<0,05). El grupo PCS presentó el mayor porcentaje de AP y el grupo PBA de PUFAs ω-6 en tejido tumoral (p<0,05). La dieta PCS+PBA produjo un aumento en la expresión de FASN (IQH-WB) (p<0,05) y un incremento en la expresión de HIF1-α (IHQ) (p<0,05). La dieta rica en Fr (PBA) aumentó el ARNm de FASN por qPCR en tejido tumoral (p<0,05). El AP40µM y la Fr2,5mM disminuyeron la apoptosis y aumentaron la viabilidad celular respecto al control en LM3(p<0,05). La combinación de AP y Fr (40µM/2,5mM) aumentó la expresión de FASN por WB (p<0,05). Dietas altas en ácido palmítico y fructosa inducen un aumento en la expresión de FASN y HIF1-α, promoviendo la proliferación celular en cáncer de mama murino. Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2023-10-19 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion application/pdf https://revistas.unc.edu.ar/index.php/med/article/view/42679 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 80 (2023): Suplemento JIC XXIV Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 80 (2023): Suplemento JIC XXIV Revista da Faculdade de Ciências Médicas de Córdoba; v. 80 (2023): Suplemento JIC XXIV 1853-0605 0014-6722 spa https://revistas.unc.edu.ar/index.php/med/article/view/42679/42864 Derechos de autor 2023 Universidad Nacional de Córdoba http://creativecommons.org/licenses/by-nc/4.0 |