title: Menadione reduced doxorubicin resistance in Ehrlich ascites carcinoma cells in vitro.
abstract: 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.
authors.affiliation: Department of Pharmacology, He-nan Institute of Medical Science, Zhengzhou, China. dli@shmu.edu.cn
authors.forename: C J
authors.initials: CJ
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: T M
authors.initials: TM
authors.lastname: Zhang
mesh_terms: 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*
chemical_list: D014812:Vitamin K; D004317:Doxorubicin; D005982:Glutathione Transferase; D005978:Glutathione