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A role for plasma membrane potential in doxorubicin--induced cytotoxicity
1Department of Surgery, Research Institute for Nuclear Medicine and Biology, Hiroshima University, Japan.
Abstract:
Using a modifier of membrane function, we have shown that plasma membrane potential plays an important role in doxorubicin (DOX) - induced cytotoxicity through its connection with cell metabolism and through its effect on drug accumulation. Membrane potential of K562 cells, measured using 3, 3'-dihexyl-oxacarbocyanine (DiOC6 (3)), was increased in the presence of non-toxic cepharanthin or N-1379 and decreased in the presence of non-toxic K252a. Correlated with the level of the potential, DOX efficacy was enhanced by cepharanthin or N-1379 and decreased by K252a associated with an increase or decrease of the percentage of cells in S-phase and of intracellular DOX accumulation.