Diazenes as modificators of drug-resistance in tumor cells

To overcome the drug resistance, which is the major obstacle in the success ful treatment of cancer patients, various compounds have been tested. Gluta thione is one of the most promising targets for modulation, in the present study, we examined the influence of five new synthesized compounds - diazen es on the reduction of the intracellular level of GSH. Further, we investig ated their ability to increase the cytotoxicity of cisplatin, vincristine a nd doxorubicin. Tn experiments human parental cervical (HeLa) and laryngeal (HEp2) carcinoma cells and their drug-resistant cell sublines (HeLaCA and CK2, respectively) were used. intracellular GSH content was examined spectr ophotometrically by the procedure developed by Tietze. The cell sensitivity to drugs was determined using a modified colorimetric MTT assay. Results s howed that the rate of reduction of GSH concentration was dependent on the cell type and the type of diazenes. We did not find a correlation between t he reduction in GSH level and increased cytotoxicity to selected anticancer drugs. Nevertheless, we found that: a) diazenes LV-35 and VZ-19 increased the cytotoxicity of cisplatin in HEp2 cells, b) diazene MG-19 potentiated t he cytotoxicity of vincristine in HEp2 cells, and c) diazene VZ-19 in HeLaC A cells. These data suggest that specific combination of diazene and antica ncer drug may be useful in the treatment of certain turner types.