Most studies indicate that modulation of
glutathione metabolism may be one of the most promising means of reversing clinical drug resistance. Five new
diazene compounds have been synthesized:
JK-279, JK-835, JK-913, JK-925 and LV-57 that should, according to their structure and biochemical properties, lower the GSH concentration. In the present study, we examined the influence of diazenes on
cisplatin resistance in human cervical (HeLa) and laryngeal
carcinoma (HEp2) cells as well as in their
cisplatin-resistant sublines (HeLaCA and CK2, respectively). Intracellular GSH content was examined spectrophotometrically by the procedure developed by Tietze. The cell sensitivity to drugs was determined using a modified colorimetric MTT assay. Results show that all examined diazenes lowered GSH concentration. This decrease was insignificant for JK-835 and JK-925 in HeLa and HeLaCA cells, and JK-925 in CK2 cells. In human cervical
carcinoma HeLa and HeLaCA cells,
JK-279 was mostly active in sensitizing the cells to
cisplatin, especially in
drug-resistant cells. JK-913, JK-835 and LV-57 reverted partially resistance to
cisplatin in HEp2 cells, while none of the diazenes was active in CK2 cells. In conclusion,
diazene JK-279 may be useful in the combined treatment (
cisplatin +
diazene) for the certain type of
cancer.