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1.
An. acad. bras. ciênc ; 73(1): 57-69, Mar. 2001. ilus, graf
Artículo en Inglés | LILACS | ID: lil-281085

RESUMEN

Multidrug resistance to chemotherapy is a major obstacle in the treatment of cancer patients. The best characterised mechanism responsible for multidrug resistance involves the expression of the MDR-1 gene product, P-glycoprotein. However, the resistance process is multifactorial. Studies of multidrug resistance mechanisms have relied on the analysis of cancer cell lines that have been selected and present cross-reactivity to a broad range of anticancer agents. This work characterises a multidrug resistant cell line, originally selected for resistance to the Vinca alkaloid vincristine and derived from the human erythroleukaemia cell K562. This cell line, named Lucena 1, overexpresses P-glycoprotein and have its resistance reversed by the chemosensitisers verapamil, trifluoperazine and cyclosporins A, D and G. Furthermore, we demonstrated that methylene blue was capable of partially reversing the resistance in this cell line. On the contrary, the use of 5-fluorouracil increased the resistance of Lucena 1. In addition to chemotherapics, Lucena 1 cells were resistant to ultraviolet A radiation and hydrogen peroxide and failed to mobilise intracellular calcium when thapsigargin was used. Changes in the cytoskeleton of this cell line were also observed


Asunto(s)
Humanos , Antineoplásicos Fitogénicos/farmacología , Resistencia a Múltiples Medicamentos , Células K562/efectos de los fármacos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Vincristina/farmacología , Resistencia a Múltiples Medicamentos/genética , Expresión Génica , Leucemia Eritroblástica Aguda/tratamiento farmacológico , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Fenotipo
2.
Experimental & Molecular Medicine ; : 174-178, 1999.
Artículo en Inglés | WPRIM | ID: wpr-158709

RESUMEN

Tanshinone II-A is a derivative of phenanthrene-quinone isolated from Salvia miltiorrhiza BUNGE, a traditional herbal medicine that is known to induce antiinflammatory, anti-oxidative and cytotoxic activity. We have examined cellular effects of Tanshione II-A on HL60 human promyelocytic leukemic cells and K562 human erythroleukemic cells. Tanshione II-A induced a dose- and time-dependent DNA fragmentation into the multiples of 180 bp and specific proteolytic cleavage of poly(ADP-ribose) polymerase in both cell lines. PI-staining and flow cytometry analysis of K562 cells following Tanshione II-A treatment showed an increase of the cells possessing hypodiploid DNA indicative of apoptotic state of cells. Caspase-3 activity was significantly increased during Tanshinone II-A treatment of both HL60 and K562 cells, whereas caspase-1 activity was not changed. These results suggest that Tanshione II-A induced HL60 and K562 cellular apoptosis that may be associated with the selective members of caspase family. Copyright 2000 Academic Press.


Asunto(s)
Humanos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Apoptosis/fisiología , Caspasas/metabolismo , Caspasas/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Activación Enzimática/efectos de los fármacos , Células HL-60/patología , Células HL-60/metabolismo , Células HL-60/efectos de los fármacos , Lamiaceae/química , Leucemia/patología , Leucemia/metabolismo , Leucemia/tratamiento farmacológico , Leucemia Eritroblástica Aguda/patología , Leucemia Eritroblástica Aguda/metabolismo , Leucemia Eritroblástica Aguda/tratamiento farmacológico , Fenantrenos/farmacología , Fenantrenos/química , Células Tumorales Cultivadas
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