Tumor development in breast cancer by activation of fatty acid synthase in diets rich in palmitic acid and fructose
Breast cancer is the first leading cause of mortality in women and is associated with genetic and epigenetic factors such as dietary compounds. In our laboratory we demonstrated that dietary polyunsaturated fatty acids (PUFAs) activate enzymes such as cyclooxygenases, lipooxygenases and other p...
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Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2022
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/39106 |
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I10-R327-article-39106 |
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ojs |
| institution |
Universidad Nacional de Córdoba |
| institution_str |
I-10 |
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R-327 |
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Revista de la Facultad de Ciencias Médicas de Córdoba |
| format |
Artículo revista |
| topic |
palmitic acid fructose breast cancer fatty acid synthase ácido palmítico fructosa cáncer de mama ácido graso sintasa (FASN) |
| spellingShingle |
palmitic acid fructose breast cancer fatty acid synthase ácido palmítico fructosa cáncer de mama ácido graso sintasa (FASN) Ferrero, V Mazo, T Barotto, NN Don, JA Sosa, LVD Rodríguez, V Quintar, AA Pasqualini, ME Tumor development in breast cancer by activation of fatty acid synthase in diets rich in palmitic acid and fructose |
| topic_facet |
palmitic acid fructose breast cancer fatty acid synthase ácido palmítico fructosa cáncer de mama ácido graso sintasa (FASN) |
| author |
Ferrero, V Mazo, T Barotto, NN Don, JA Sosa, LVD Rodríguez, V Quintar, AA Pasqualini, ME |
| author_facet |
Ferrero, V Mazo, T Barotto, NN Don, JA Sosa, LVD Rodríguez, V Quintar, AA Pasqualini, ME |
| author_sort |
Ferrero, V |
| title |
Tumor development in breast cancer by activation of fatty acid synthase in diets rich in palmitic acid and fructose |
| title_short |
Tumor development in breast cancer by activation of fatty acid synthase in diets rich in palmitic acid and fructose |
| title_full |
Tumor development in breast cancer by activation of fatty acid synthase in diets rich in palmitic acid and fructose |
| title_fullStr |
Tumor development in breast cancer by activation of fatty acid synthase in diets rich in palmitic acid and fructose |
| title_full_unstemmed |
Tumor development in breast cancer by activation of fatty acid synthase in diets rich in palmitic acid and fructose |
| title_sort |
tumor development in breast cancer by activation of fatty acid synthase in diets rich in palmitic acid and fructose |
| description |
Breast cancer is the first leading cause of mortality in women and is associated with genetic and epigenetic factors such as dietary compounds. In our laboratory we demonstrated that dietary polyunsaturated fatty acids (PUFAs) activate enzymes such as cyclooxygenases, lipooxygenases and other peroxidases implicated in the regulation of carcinogenesis. 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 this enzyme 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 breast cancer 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 breast cancer development.
BALB/c mice (n=40) were divided in four 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). After 90 days mice were inoculated with murine breast adenocarcinoma LM3 cells (1x106cell). In this model we evaluated tumor volume (with calimeter), lipid profile (gas chromatography: GC), FASN expression (Western Blot and immunohistochemistry) and tumor histology (H/E). For the in vitro model, cultured LM3 cells were treated with PA (40µM-50µM) and/or Fr (2.5µM) for 24hs. We evaluated viability (resazurin), apoptosis (Hoechst), lipid profile (GC), FASN expression (Western Blot). Three replicates were minimally performed by experiment and analyzed by ANOVA.
The PCS+PBA diet produced an increment in tumor growth, infiltration, necrosis and FASN expression (p<0.05). FASN expression was increased after PA and Fr (40/2.5 µM) treatment in LM3 cells. The PCS group presented the highest percentage of PA and the PBA a high percentage of ω-6 PUFAs in membranes with respect to the other experimental groups. The combination of PA 40µM and Fr 2.5µM treatment decreased LM3 apoptotic cells and PA 40µM increased cell viability.
Diets high in palmitic acid and fructose induce tumor development in murine breast cancer, mediated by an increment in FASN enzyme expression regulated by hypoxia.
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| publisher |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2022 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/39106 |
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I10-R327-article-391062024-04-15T16:14:45Z Tumor development in breast cancer by activation of fatty acid synthase in diets rich in palmitic acid and fructose Desarrollo tumoral en cáncer de mama por activación de ácido graso sintasa en dietas ricas en ácido palmítico y fructosa Ferrero, V Mazo, T Barotto, NN Don, JA Sosa, LVD Rodríguez, V Quintar, AA Pasqualini, ME palmitic acid fructose breast cancer fatty acid synthase ácido palmítico fructosa cáncer de mama ácido graso sintasa (FASN) Breast cancer is the first leading cause of mortality in women and is associated with genetic and epigenetic factors such as dietary compounds. In our laboratory we demonstrated that dietary polyunsaturated fatty acids (PUFAs) activate enzymes such as cyclooxygenases, lipooxygenases and other peroxidases implicated in the regulation of carcinogenesis. 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 this enzyme 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 breast cancer 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 breast cancer development. BALB/c mice (n=40) were divided in four 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). After 90 days mice were inoculated with murine breast adenocarcinoma LM3 cells (1x106cell). In this model we evaluated tumor volume (with calimeter), lipid profile (gas chromatography: GC), FASN expression (Western Blot and immunohistochemistry) and tumor histology (H/E). For the in vitro model, cultured LM3 cells were treated with PA (40µM-50µM) and/or Fr (2.5µM) for 24hs. We evaluated viability (resazurin), apoptosis (Hoechst), lipid profile (GC), FASN expression (Western Blot). Three replicates were minimally performed by experiment and analyzed by ANOVA. The PCS+PBA diet produced an increment in tumor growth, infiltration, necrosis and FASN expression (p<0.05). FASN expression was increased after PA and Fr (40/2.5 µM) treatment in LM3 cells. The PCS group presented the highest percentage of PA and the PBA a high percentage of ω-6 PUFAs in membranes with respect to the other experimental groups. The combination of PA 40µM and Fr 2.5µM treatment decreased LM3 apoptotic cells and PA 40µM increased cell viability. Diets high in palmitic acid and fructose induce tumor development in murine breast cancer, mediated by an increment in FASN enzyme expression regulated by hypoxia. El cáncer de mama es la primera causa de mortalidad en mujeres, está asociado no sólo a factores genéticos sino epigenéticos, como los dietarios. En nuestro laboratorio demostramos que lípidos dietarios poliinsaturados (PUFAs) activan enzimas como las ciclooxigenasas, lipooxigenasas y otras peroxidasas involucradas en la regulación de la carcinogénesis. La ácido graso sintasa (FASN) participa en la lipogénesis de novo, catalizando la síntesis de ácidos grasos endógenos. En estadios tempranos de carcinogénesis, la activación de FASN es mediada por hipoxia, inducida por altas concentraciones de azúcares y grasas. Su sobreexpresión está asociada a un mal pronóstico. Sin embargo, aún se desconoce la regulación dietaria de FASN en el desarrollo de cáncer de mama. El objetivo fue evaluar si la variación en ácido palmítico (AP) y fructosa (Fr) dietarios regula la expresión de FASN mediada por hipoxia en el desarrollo de cáncer de mama murino. Se utilizó un modelo in vivo: ratones BALB/c (n=40) divididos en grupos dietarios, CONTROL (6%aceite de maíz+30%fructosa), PCS (20%aceite de palma+15%fructosa), PBA (20%aceite de maíz+45% fructosa) y PCS+PBA (20%aceite de palma+45%fructosa), los cuales fueron inoculados a los 90 días con células LM3 de adenocarcinoma de mama murino (1x106cél). Se evaluó: volumen tumoral (calímetro), perfil lipídico (cromatografía gaseosa: GC), expresión de FASN (Western Blot e inmunohistoquímica) e histología (H/E). In vitro: células LM3 fueron tratadas con AP (40µM-50µM) y/o Fr (2,5µM) por 24hs. Se evaluó viabilidad (resazurina), apoptosis (Hoechst), perfil lipídico (GC), expresión de FASN (Western Blot). Los experimentos se repitieron mínimamente tres veces y se analizaron por ANOVA. La dieta PCS+PBA produjo un aumento en el crecimiento, infiltración, necrosis tumoral y expresión de FASN (p<0,05). El grupo PCS presentó el mayor porcentaje de AP y el PBA un alto porcentaje de PUFAs ω-6 en membranas respecto a los demás grupos experimentales. El AP 40µM y la Fr 2,5µM disminuyeron la apoptosis. Se observó un aumento en la viabilidad celular con AP 40µM. La combinación de AP y Fr (40/2,5 µM) aumentó la expresión de FASN. El AP más Fr dietarios indujeron un aumento en el crecimiento tumoral que se correlacionó con la sobreexpresión de FASN. Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2022-10-26 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion texto https://revistas.unc.edu.ar/index.php/med/article/view/39106 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 79 No. Suplemento JIC XXIII (2022): Suplemento JIC XXIII Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 79 Núm. Suplemento JIC XXIII (2022): Suplemento JIC XXIII Revista da Faculdade de Ciências Médicas de Córdoba; v. 79 n. Suplemento JIC XXIII (2022): Suplemento JIC XXIII 1853-0605 0014-6722 http://creativecommons.org/licenses/by-nc/4.0 |