Menadione reduced doxorubicin resistance in Ehrlich ascites carcinoma cells in vitro.
OBJECTIVE
To study the effect of menadione (Men) reducing doxorubicin (Dox) resistance in Ehrlich ascites carcinoma (EAC) cells resistant to Dox (EAC/Dox cells).


METHODS
Glutathione (GSH) content and membrane fluidity were measured by fluorometric assay and fluorescence depolarization assay, respectively. Glutathione S-transferase (GST) activity was measured with 1-chloro-2,4-dinitrobenzene as the substrate. Cell viability was determined by 3-(4, 5-dimethylthiazol)-2, 5-diphenyltetrazolium bromide assay.


RESULTS
GSH content, GST activity, and membrane fluidity in EAC/Dox cells were higher than those in EAC cells (P < 0.01). The IC50 (95% confidence limits) for Dox on EAC/Dox cell was 22.3 (15.8-28.8) mg.L-1. Relative resistance of Dox in EAC/Dox cells was 42-fold. Pretreatment of EAC/Dox cells with Men 5 or 10 mg.L-1 decreased intracellular GSH content (P < 0.01). Men 1 mg.L-1 had no obvious effect on GSH content in EAC/Dox cells (P > 0.05), but decreased the elevated membrane fluidity efficiently (P < 0.05). Men had no obvious effect on GST activity in EAC/Dox cells (P > 0.05). IC50 of Dox was reduced to 9.6 (7.8-11.3), 6.0 (2.8-9.2), or 5.3 (3.9-6.7) mg.L-1 in EAC/Dox cells pretreated with Men 1, 5, or 10 mg.L-1.


CONCLUSIONS
Men reduced Dox resistance effectively due in part to its depletion of GSH content in EAC/Dox cells.
Xu
C J
CJ
Department of Pharmacology, He-nan Institute of Medical Science, Zhengzhou, China. dli@shmu.edu.cn
Zhang
Y
Y
Wang
J
J
Zhang
T M
TM
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology*; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014812:Vitamin K / Q000494:pharmacology*
D014812:Vitamin K; D004317:Doxorubicin; D005982:Glutathione Transferase; D005978:Glutathione