Reversal of Multidrug Resistance in Human Leukemia K562 by Tamolarizine, a Novel Calcium Antagonist

Abstract

A new type of organic Ca²⁺ channel blocker, tamolarizine, was examined for its reversing effect on multidrug-resistant tumor cells.Tamolarizine synergistically potentiated the cytotoxicity of doxorubicin for doxorubicin-resistant K562 cells(K562/DXR)at a concentration of 0.1-10μM, but had hardly any synergistic effects in the parental cell line(K562)at the same concentration.Moreover, tamolarizine inhibits the P-glycoprotein pump-efflux activity in a dose-related manner and reduces the expression of the immunoreactive P-glycoprotein in K562/DXR cells as evaluated by cytofluorimetric assay.These results indicate that tamolarizine reverses the multidrug-resistance phenotype through direct interaction with P-gylcoprotein.