RESUMEN

This study shows the effect of pterostilbene on intracellular neutral lipid accumulation in MCF-7 breast cancer cells leading to growth arrest and autophagy. On exposing the breast cancer cells with 30 µM pterostilbene for 72 h there was almost 2-folds increase in neutral lipids and triglycerides. Also the phytochemical caused a 4-folds increase in the expression of adipogenic differentiation marker c/EBPα. Further, pterostilbene inhibited 3ß-hydroxylsterol-Δ(7)-reductase, the enzyme which catalyzes the last step conversion of 7-dehydrocholesterol to cholesterol, and thereby causes the intracellular accumulation of the former sterol. These results were associated with over-expression of oxysterol binding protein homologue and liver X receptor (LXR) by ~7-folds. Pterostilbene also caused a simultaneous increase in the expression autophagic marker proteins Beclin 1 and LC3 II (microtubule-associated protein 1 light chain 3) by approximately 6-folds, which leads to an alternative pathway of autophagy. These effects were observed in association with the loss of mitotic and metastatic potential of MCF-7 cells which was abolished in the presence of catalase (ROS scavenger) or 3MA (autophagic inhibitor). Thus the present data shows that the long term exposure to pterostilbene causes growth arrest in MCF-7 cells which may be due to differentiation of the mammary carcinoma cells into normal epithelial cell like morphology and activation of autophagy.

Asunto(s)

Autofagia/efectos de los fármacos , Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Estilbenos/farmacología , Proteínas Reguladoras de la Apoptosis/agonistas , Proteínas Reguladoras de la Apoptosis/genética , Beclina-1 , Biomarcadores/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Proteínas Potenciadoras de Unión a CCAAT/agonistas , Proteínas Potenciadoras de Unión a CCAAT/genética , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Deshidrocolesteroles/antagonistas & inhibidores , Deshidrocolesteroles/metabolismo , Femenino , Humanos , Receptores X del Hígado , Proteínas de la Membrana/agonistas , Proteínas de la Membrana/genética , Proteínas Asociadas a Microtúbulos/agonistas , Proteínas Asociadas a Microtúbulos/genética , Receptores Nucleares Huérfanos/agonistas , Receptores Nucleares Huérfanos/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/antagonistas & inhibidores , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/genética , Especies Reactivas de Oxígeno/metabolismo , Receptores de Esteroides/agonistas , Receptores de Esteroides/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Triglicéridos/biosíntesis