Inhibition of membrane redox activity by rhein and adriamycin in human glioma cells.
The effect of the combination of adriamycin (ADM) with the anti-inflammatory drug rhein (RH) on the membrane redox activity in human glioma cells was investigated. RH, although less effective than ADM, inhibits ferricyanide reduction by human glioma cells in a dose-dependent manner as well as ferricyanide-induced proton release. The inhibition of the plasma membrane redox system might represent a further mechanism by which RH, other than ATP depletion, affects cell survival. The analysis of the interaction between ADM and RH, performed with the isobolar method, demonstrates a strong synergic response, probably due to an effect on different sites of action. The synergism of the ADM-RH association allows us to achieve a pre-established extent of inhibition with ADM concentrations much lower than with ADM alone. RH might, therefore, represent a very useful tool to improve the therapeutic index of ADM and to lower its general toxicity.
Fanciulli
M
M
Laboratory for Cell Metabolism and Pharmacokinetics, Regina Elena Institute for Cancer Research, Rome, Italy.
Gentile
F P
FP
Bruno
T
T
Paggi
M G
MG
Benassi
M
M
Floridi
A
A
D000880:Anthraquinones / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D005292:Ferricyanides / Q000737:chemistry; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000880:Anthraquinones; D005292:Ferricyanides; C007931:hexacyanoferrate III; D004317:Doxorubicin; D009247:NADH, NADPH Oxidoreductases; C020491:rhein