Action mechanism of idarubicin (4-demethoxydaunorubicin) as compared with daunorubicin in leukemic cells.

To characterize a new anthracycline agent, idarubicin (4-demethoxydaunorubicin) and to establish its reasonable and appropriate use in the chemotherapy of acute leukemia, we examined its mode of action and compared it with the results obtained for daunorubicin. Idarubicin was shown to have the characteristic features of the action mechanism of anthracyclines, such as having a strong binding capacity to DNA, in terms of frequency and efficiency and reducing the template activity of DNA by binding to DNA or inducing DNA strand breaks in leukemic cells and inhibiting the DNA polymerase reaction. Idarubicin was superior to daunorubicin in terms of intracellular accumulation and binding capacity to DNA, which may result in idarubicin having much stronger activity in inducing DNA strand breaks than daunorubicin. These excellent properties of idarubicin were considered to explain idarubicin having stronger antileukemic effects than daunorubicin. The efficacy of idarubicin in multidrug-resistant cells is also discussed.