title: A role for plasma membrane potential in doxorubicin--induced cytotoxicity.
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.
authors.affiliation: Department of Surgery, Research Institute for Nuclear Medicine and Biology, Hiroshima University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nishiyama
authors.forename: K
authors.initials: K
authors.lastname: Aogi
authors.forename: S
authors.initials: S
authors.lastname: Saeki
authors.forename: R
authors.initials: R
authors.lastname: Kim
authors.forename: K
authors.initials: K
authors.lastname: Kuroi
authors.forename: Y
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Toge
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D044182:Benzylisoquinolines; D002227:Carbazoles / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D026121:Indole Alkaloids; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D008564:Membrane Potentials / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D052117:Benzodioxoles
chemical_list: D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D044182:Benzylisoquinolines; D002227:Carbazoles; D004317:Doxorubicin; D026121:Indole Alkaloids; D011493:Protein Kinase C; C006947:cepharanthine; D052117:Benzodioxoles; C049985:staurosporine aglycone