Tsuruo T et al. - In a study to assess the use of NC-190 against multidrug-resistant human and mouse tumor cells in vitro and in vivo, it was shown that NC-190 is not transported out of resistant cells by P-glycoprotein and it inhibits DNA topoisomerase II activity in the cells, resulting in its likely effectiveness against various multidrug-resistant tumor cells Methods
NC-190 was tested against multidrug-resistant human and mouse tumor cells in vitro and in vivo
Results
When vincristine (VCR)-resistant P388 leukemia-bearing mice were treated with an optimal dose of NC-190, 4 of 6 mice were cured, whereas treatment of mice with VCR resulted in a marginal increase in life span
The compound showed chemotherapeutic effect against Adriamycin-resistant P388 leukemia-bearing mice and was effective against various multidrug-resistant human and murine tumor cells in vitro
Its cytotoxicity to multidrug-resistant K562 cells was not enhanced by the addition of verapamil
Accumulation of NC-190 in multidrug-resistant K562 cells was slightly lower than that observed in sensitive K562 cells; the compound did not efficiently inhibit the binding of VCR to the plasma membrane of resistant cells, indicating that NC-190 has little affinity for P-glycoprotein
NC-190 inhibited the activity of DNA topoisomerase II
See all
