Potentiation of Doxorubicin-Induced Apoptosis of Resistant Mouse Leukaemia Cells by Ivermectin

Abstract

The apoptosis and cell cycle effect of doxorubicin were evaluated in the presence and absence of ivermectin in mouse doxorubicin-resistant P388 leukaemia cells. Ivermectin (2 μM) increased the sensitivity to doxorubicin of multidrug resistant (MDR) mouse leukemic P388 cells and significantly enhanced the apoptosis and intracellular accumulation of doxorubicin in resistant cells, but had no effect on parent cells. Using the fluorescent potential probe, 3,3′-dihexyl-oxacarbocyanine, we found that ivermectin induced a plasma membrane potential increase in resistant cells. Ivermectin also enhanced doxorubicin-induced G2/M blockade of the cell cycle in resistant cells. It is possible that ivermectin could reverse resistance by direct interaction with the P-glycoprotein or other components of the altered MDR cell membrane.