title: Cytotoxic effects of diazenes on tumor cells in vitro.
abstract: BACKGROUND
  We have shown previously that diazenecarboxamides (diazenes) were cytotoxic for several tumor cell lines. Their target seems to be the intracellular glutathione (GSH). To improve the solubility and biological activity of these drugs, new compounds have been synthesized. In the present study we examined the cytotoxic effect of six new diazenes: BR-25, UP-39, UP-11, JK-1024, RL-514 and RL-625.
  
  
  METHODS
  The cytotoxicity of diazenes was tested on nine human tumor cell lines: laryngeal carcinoma HEp2 cells, cervical carcinoma HeLa cells, mammary carcinoma MCF-7 cells, breast adenocarcinoma SK-BR-3 cells, and glioblastoma A1235 cells and their four drug-resistant cell lines. Cytotoxicity was determined using the colorimetric MTT assay. The intracellular GSH content (following the treatment with diazenes) was examined spectrophotometrically in human cervical carcinoma cells by the procedure developed by Tietze.
  
  
  RESULTS
  Results show that diazene UP-39 was mostly efficient, significantly reducing the cell survival of all nine cell lines examined, including four drug-resistant cell lines. Diazenes UP-11, RL-514 and BR-25 given in the highest concentrations decreased the survival of some examined cell lines, but to less than 50%. Diazenes RL-625 and JK-1024 had no influence on the cell survival. None of the examined diazenes significantly influenced the intracellular level of GSH.
  
  
  CONCLUSIONS
  Our results suggest that diazene UP-39 may be a promising new drug for the treatment of tumors and encourage further research on this compound.
authors.affiliation: Department of Molecular Genetics, Ruder Bosković Institute, University of Zagreb, Croatia.
authors.forename: Dubravka
authors.initials: D
authors.lastname: Moskatelo
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Benjak
authors.forename: Vibor
authors.initials: V
authors.lastname: Laketa
authors.forename: Slovenko
authors.initials: S
authors.lastname: Polanc
authors.forename: Janez
authors.initials: J
authors.lastname: Kosmrlj
authors.forename: Maja
authors.initials: M
authors.lastname: Osmak
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm; D005260:Female; D005562:Formazans; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007094:Imides / Q000494:pharmacology*; D066298:In Vitro Techniques; D013778:Tetrazolium Salts; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D005562:Formazans; D007094:Imides; D013778:Tetrazolium Salts; C079782:MTT formazan; D005978:Glutathione; C038867:diazene