Enhancement of doxorubicin activity in multidrug-resistant cells by mefloquine.

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Fujita R, Ishikawa M, Takayanagi M, Takayanagi Y, Sasaki K

Enhancement of doxorubicin activity in multidrug-resistant cells by mefloquine.

Methods Find Exp Clin Pharmacol. 2000 Jun;22(5):281-4.

PubMed ID

11031728 [ View in PubMed

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Abstract

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 microM, 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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Mefloquine	P-glycoprotein 1	Protein	Humans	Unknown	Substrate Inhibitor	Details