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Methods and Findings
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Methods Find Exp Clin Pharmacol 2000, 22(5): 281
ISSN 0379-0355
Copyright 2000 Clarivate Analytics
CCC: 0379-0355
DOI: 10.1358/mf.2000.22.5.796646
Enhancement of doxorubicin activity in multidrug-resistant cells by mefloquine
Fujita, R., Ishikawa, M., Takayanagi, M., Takayanagi, Y., Sasaki, K.
We studied the effect of the antimalarial drug mefloquine on the resistance of K562 cells to doxorubicin. Mefloquine synergistically potentiated the cytotoxicity of doxorubicin for doxorubicin-resistant K562 cells (K562/DXR) at a concentration of 0.5-3 mcM, but had hardly any synergistic effect in the parental cell line (K562) at the same concentration. Mefloquine was more potent than verapamil, a known modulator of multidrug-resistance. Since doxorubicin resistance in these cells is associated with the expression of high levels of P-glycoprotein, we evaluated the effect of mefloquine and of P-glycoprotein activity in cytofluorographic efflux experiments with the fluorescent dye rhodamine 123. Our results indicate that mefloquine inhibits the P-glycoprotein pump-efflux activity in a dose-related manner. Moreover, mefloquine reduces the expression of the immunoreactive P-glycoprotein in K562/DXR cells as evaluated by cytofluorimetric assay. Taken together, the results indicate that mefloquine reverses the multidrug-resistance phenotype through direct interaction with P-glycoprotein.

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