Investigations of the action of the antitumour drug adriamycin on tumour cell membrane functions--I.
The membrane potential of L1210 murine leukemia cells was assessed by use of the tritiated lipophilic cation probe triphenylmethylphosphonium bromide. The potassium equilibrium potential of the cells was found to be -71 +/- 7 mV. The resting membrane potential was partly dissipated by the protonophore m-chlorocarbonylcyanidephenylhydrazone (10 microM), but was unaffected by ouabain (1 mM) and apparently by the calcium ionophore A23187 (2.5 microM). Monensin (20 microM) caused a hyperpolarization which, since it was blocked by ouabain, was presumed to be brought about by activation of the Na+K+-ATPase via an elevated cytoplasmic Na+ concentration. Adriamycin at concentrations as high as 5 X 10(-4) M brought about no change in the resting potential of the cells. Also, cytotoxic concentrations of adriamycin, unlike ouabain, had no effect on rubidium-86 transport into L1210 cells, nor upon a monensin-induced increased in rubidium-86 uptake. The results suggest that although adriamycin is capable of interaction with the plasma membrane, and may exert its cytotoxicity at this locus, changes in ion flux mediated by Na+K+-ATPase or those capable of changing the membrane potential do not appear to be implicated in its mechanism of action.
Chahwala
S B
SB
Hickman
J A
JA
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008985:Monensin / Q000494:pharmacology; D009861:Onium Compounds / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D014320:Triphenylmethyl Compounds / Q000378:metabolism
D009861:Onium Compounds; D014320:Triphenylmethyl Compounds; C011561:triphenylmethylphosphonium; D000001:Calcimycin; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D010042:Ouabain; D004317:Doxorubicin; D008985:Monensin; D000254:Sodium-Potassium-Exchanging ATPase