Evaluación in-vitro del efecto de la curcumina y curcumina dietil succinato sobre la viabilidad y producción de il-6 en cultivos celulares de cáncer de mama
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Rev.Cs.Farm. y Bioq.
Abstract
La curcumina es un polifenol usado como colorante natural obtenido del Turmeric (Curcuma Longa) oriundo de la India. Diferentes investigaciones han identificado a la curcumina como el metabolito con mayor actividad del turmeric (Curcuma Longa); estudios in vitro demuestran la actividad anti-inflamatoria, anti-oxidante y anti-cancerí-gena de esta sustancia. Esta investigación se efectuó en el Laboratorio de Farmacología del Massachusetts College of Pharmacy and Health Sciences University, Boston, Estados Unidos en el periodo mayo-agosto 2014, con el fin de evaluar la actividad de la curcumina y curcumina dietil succinato (compuesto sintético análogo a la curcumina con mayor estabilidad), sobre la viabilidad celular y uno de los mecanismos de proliferación y metástasis del cáncer de mama, el cual es la producción de IL-6. Se usaron cultivos celulares de cáncer de mama (línea celular MDA-MB 231) los cuales fueron tratados con curcumina y curcumina dietil succinato en concentraciones de 1 uM, 3 uM y 10 uM, en ambos casos. Posterior a la incubación, durante 24 horas, se determinó la viabilidad de los cultivos celulares tratados utilizando los ensayos de exclusión de azul de tripán y citotoxicidad por MTS, y se midió la concentración de IL-6 mediante ELISA (Ensayo por Inmunoabsorción Ligado a Enzima). Los resultados demostraron cambios en la morfología de los cultivos celulares, disminución en la proliferación de las células cancerígenas (viabilidad) con ambos tipos de curcumina en relación al control, siendo la viabilidad de los cultivos tratados con curcumina menor que la observada con la curcumina dietil succinato. En relación a la producción de IL-6 se corroboró que las células cancerígenas producen concentraciones muy elevadas de esta citocina (90-98 pg/ml, valores correspondientes a los controles empleados), los cuales fueron visiblemente disminuidos luego de incubar las células con curcumina y curcumina dietilsuccinato en concentraciones de 1, 3 y 10 uM. También se demostró estadísticamente que la curcumina produjo una mayor reducción en los niveles de IL-6 que la curcumina dietil succinato en concentraciones de 3 y 10 uM, sin embargo a 1 uM la curcumina sintética mostró mayor eficacia. Al relacionar la disminución de la viabilidad celular producida por ambas curcuminas, con la producción de IL-6, se observó que no existe una relación directa entre tales parámetros ya que a pesar de la significativa disminución en la proliferación celular inducida por las curcuminas, la producción de IL-6 en los cultivos celulares continuó siendo superior a los valores observados en células sanas. Se concluyó que las curcuminas modifican la morfología celular de las células cancerígenas, disminuyendo su viabilidad y la producción de IL-6, no habiéndose encontrado una relación directa entre estas dos últimas variables.
Curcumin is a polyphenol used as natural dye obtained from Turmeric (Curcuma Longa) which is native from India. Different studies have identified the curcumin as the most active metabolite of turmeric (Curcuma Longa); in-vitro studies demonstrate anti-inflammatory, anti-oxidant and anti-cancer activity of curcumin. This research was carried out in the Laboratory of Farmacology from the Massachusetts College of Pharmacy and Health Sciences University, Boston, USA in the period from May to August in order to assess the activity of curcumin and curcumin diethyl succinate (analogous synthetic compound of curcumin with increased stability) over the cellular viability and one of the mechanisms of proliferation and metastasis of breast cancer, which is the IL-6 production. We used cell cultures of breast cancer (MDA-MB 231 cell line) treated with curcumin and curcumin diethyl succinate in different concentrations: 1 uM, 3 uM and 10 uM in both cases. After incubation of 24 hours, it was determined the cellular viability with tripan blue and MTS assay, the concentration of IL-6 was determined by ELISA (Enzyme Linked Assay by immunoabsorption). Our results showed a decrease in the proliferation of cancer cells (viability) with both curcumins compared with the control group, being the viability of the cultures treated with curcumin lower than the cells with diethyl succinate curcumin. In relation to the IL-6 production, itwas confirmed that cancer cells produce very high concentrations of this cytokine (90-98 pg / ml, values corresponding to the controls used), which were visibly reduced after cell incubation with curcumin and diethyl succinate curcumin at concentrations of 1, 3 and 10 uM. Also, itwasshown statistically that curcumin produced a greater reduction in IL-6 levels than the diethyl succinate curcumin in concentrations of 3 and 10 uM, however at 1 uM the synthetic curcumin was more efficient. When we relate the reduc-tion of cell viability caused by both curcumins, with the production of IL-6, itwas observed that there is not a direct relationship between such parameters because even with the significant decrease in cell proliferation induced by curcumins, IL-6 production in cell cultures remained higher than the values observed in healthy cells. Itwas concluded that curcumins modify cell morphology of cancer cells, reducing their viability and IL-6 production, nothaving found a direct relationship between these two variables.
Curcumin is a polyphenol used as natural dye obtained from Turmeric (Curcuma Longa) which is native from India. Different studies have identified the curcumin as the most active metabolite of turmeric (Curcuma Longa); in-vitro studies demonstrate anti-inflammatory, anti-oxidant and anti-cancer activity of curcumin. This research was carried out in the Laboratory of Farmacology from the Massachusetts College of Pharmacy and Health Sciences University, Boston, USA in the period from May to August in order to assess the activity of curcumin and curcumin diethyl succinate (analogous synthetic compound of curcumin with increased stability) over the cellular viability and one of the mechanisms of proliferation and metastasis of breast cancer, which is the IL-6 production. We used cell cultures of breast cancer (MDA-MB 231 cell line) treated with curcumin and curcumin diethyl succinate in different concentrations: 1 uM, 3 uM and 10 uM in both cases. After incubation of 24 hours, it was determined the cellular viability with tripan blue and MTS assay, the concentration of IL-6 was determined by ELISA (Enzyme Linked Assay by immunoabsorption). Our results showed a decrease in the proliferation of cancer cells (viability) with both curcumins compared with the control group, being the viability of the cultures treated with curcumin lower than the cells with diethyl succinate curcumin. In relation to the IL-6 production, itwas confirmed that cancer cells produce very high concentrations of this cytokine (90-98 pg / ml, values corresponding to the controls used), which were visibly reduced after cell incubation with curcumin and diethyl succinate curcumin at concentrations of 1, 3 and 10 uM. Also, itwasshown statistically that curcumin produced a greater reduction in IL-6 levels than the diethyl succinate curcumin in concentrations of 3 and 10 uM, however at 1 uM the synthetic curcumin was more efficient. When we relate the reduc-tion of cell viability caused by both curcumins, with the production of IL-6, itwas observed that there is not a direct relationship between such parameters because even with the significant decrease in cell proliferation induced by curcumins, IL-6 production in cell cultures remained higher than the values observed in healthy cells. Itwas concluded that curcumins modify cell morphology of cancer cells, reducing their viability and IL-6 production, nothaving found a direct relationship between these two variables.
Description
Vol. 3, No. 1