Diazenes: modificators of tumor cell resistance to cisplatin

Most studies indicate that modulation of glutathione metabolism may be one of the most promissing means of reversing clinical drug resistance. Five ne w diazene compounds have been synthesized: JK-279, JK-835, JK-913, JK-925 a nd LV-57 that should, according to their structure and biochemical properti es, lower the GSH concentration. In the present study, we examined the infl uence of diazenes on cisplatin resistance in human cervical (HeLa) and lary ngeal carcinoma (HEp2) cells as well as in their cisplatin-resistant sublin es (HeLaCA and CK2, respectively). Intracellular GSH content was examined s pectrophotometrically by the procedure developed by Tietze. The cell sensit ivity to drugs was determined using a modified colorimetric MTT assay. Resu lts show that all examined diazenes lowered GSH concentration. This decreas e 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 dru g-resistant cells. JK-913, JK-835 and LV-57 reverted partially resistance t o cisplatin in HEp2 cells, while none of the diazenes was active in CK2 cel ls. In conclusion, diazene JK-279 may be useful in the combined treatment ( cisplatin + diazene) for the certain type of cancer.