Calcium, calmodulin, and protein content of adriamycin-resistant and -sensitive murine leukemic cells

Anticalmodulin and calcium channel blockers have been shown to reverse Adriamycin resistance by reducing the drug efflux from resistant cells. Since cellular calcium and calmodulin levels are probably related to these effects, we have measured the total, membrane-bound, and intracellular calcium levels in Adriamycin-resistant (P388/R) and -sensitive (P388/S) leukemia cells. In P388/R cells, total calcium was approximately 1.4-fold higher than that of P388/S cells. Membrane-bound and intracellular calcium levels were also higher in P388/R cells. No major difference was observed in the calmodulin content of these cells. The P388/R cells had a higher (approximately 1.4-fold) protein content. When calculated on the basis of per unit protein, P388/S and P388/R cells had similar total calcium but a higher intracellular free calcium and calmodulin content in P388/S cells. Thus our studies suggested that the lower drug efflux and increased drug retention in P388/R cells may not be related to calcium and calmodulin levels but may be due to some other membrane-related factors.