Functional and morphological characterization of leukemic cells sensitive and resistant to doxorubicin
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2019-06-28
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Jaén: Universidad de Jaén
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[ES]El desarrollo de resistencia a los medicamentos contra el cáncer es una de las principales barreras en el tratamiento del cáncer. Este fenómeno está directamente relacionado con la expresión de transportadores específicos que están involucrados en la protección de las células neoplásicas de las moléculas dañinas y conduce a la resistencia a un amplio espectro de medicamentos con diferentes estructuras y diferentes objetivos, los llamados fármacos o MDR. Por lo tanto, para mejorar la terapia contra el cáncer, es importante comprender los cambios fenotípicos que ocurren durante su inicio para diseñar correctamente nuevas moléculas capaces de mostrar la capacidad de revertir las células al fenotipo sensible, con o sin una citotoxicidad intrínseca. En la línea celular de cáncer de colon LoVo, el fenotipo MDR, inducido por exposición a la doxorrubicina , se caracteriza por una proliferación celular más lenta y un mayor contenido de magnesio. Para evaluar si estos cambios podrían estar relacionados con la aparición de MDR, la línea celular leucémica humana se estudiaron HL60 sensible (HL60-S) y resistente a la doxorrubicina (HL60-R).Dimensión celular , curva de crecimiento, distribución del ciclo celular, potencial mitocondrial fueron evaluados también. En estas células, de diferente histogénesis, el fenotipo MDR se caracteriza por un crecimiento más lento , mayor dimensión y, curiosamente, un aumento en el contenido de ADN. La cantidad de magnesio intracelular también fue mayor, lo que favoreció la hipótesis de que estos cambios son característicos del fenotipo MDR.
[EN]The development of resistance to anticancer drugs is one of the main barriers in cancer treatment. This phenomenon is directly linked to the expression of specific transporters that are involve in protection of neoplastic cells from harmful molecules and leads to resistance to a wide spectrum of drugs with different structures and different targets, the so called Multi-Drug-Resistance or MDR. Therefore, to improve cancer therapy, it is important to understand the phenotypic changes that occur during its onset to correctly design new molecules able to show the capability to revert the cells to the sensitive phenotype, with or without an intrinsic cytotoxicity. In the colon cancer cell line LoVo, the MDR phenotype, induced by Doxorubicin exposure, is characterized by slower cell proliferation and increased magnesium content. To evaluate if these changes could be linked to MDR onset, the human leukemic cell line HL60 sensitive (HL60-S) and resistant to doxorubicin (HL60-R) were studied. Cellular dimension, growth curve, cell cycle distribution, mitochondrial potential were evaluated. Also in these cells, of different histogenesis, MDR phenotype is characterized by a slower growth rate, increased dimension and, interestingly, an increase in DNA content respect to the sensitive one. The amount of intracellular magnesium was higher too, supporting the hypothesis that these changes are characteristic of MDR phenotype.
[EN]The development of resistance to anticancer drugs is one of the main barriers in cancer treatment. This phenomenon is directly linked to the expression of specific transporters that are involve in protection of neoplastic cells from harmful molecules and leads to resistance to a wide spectrum of drugs with different structures and different targets, the so called Multi-Drug-Resistance or MDR. Therefore, to improve cancer therapy, it is important to understand the phenotypic changes that occur during its onset to correctly design new molecules able to show the capability to revert the cells to the sensitive phenotype, with or without an intrinsic cytotoxicity. In the colon cancer cell line LoVo, the MDR phenotype, induced by Doxorubicin exposure, is characterized by slower cell proliferation and increased magnesium content. To evaluate if these changes could be linked to MDR onset, the human leukemic cell line HL60 sensitive (HL60-S) and resistant to doxorubicin (HL60-R) were studied. Cellular dimension, growth curve, cell cycle distribution, mitochondrial potential were evaluated. Also in these cells, of different histogenesis, MDR phenotype is characterized by a slower growth rate, increased dimension and, interestingly, an increase in DNA content respect to the sensitive one. The amount of intracellular magnesium was higher too, supporting the hypothesis that these changes are characteristic of MDR phenotype.