Blockade of MDR1 by either XR9576 or electrical stimulation increases doxorubicin uptake. Calcein stains (green fluorescence) cells that retain intact membrane structure, but it does not label dead cells and is rapidly lost under conditions that cause cell lyses. Doxorubicin (in red) is normally extruded by drug resistant mechanisms and thus enters untreated cells reluctantly. Note that exposure to either MDR blocker or electrical stimulation achieved a greater uptake of red fluorescent doxorubicin and dramatically decreased the number of viable cells (in green). Small diagram: In viable cells, hydrolysis of Calcein-AM by intracellular esterases produces fluorescent calcein that is retained in the cell cytoplasm. Exposure to AC stimulation increases doxorubicin cytotoxicity thus compromising cell viability and esterases activity.