EXPERIMENTAL ANTITUMOR-ACTIVITY OF THE CE(IV)-MITOXANTRONE COMPLEX AND ITS INTERACTION WITH DEOXYRIBONUCLEIC-ACID

The Ce(IV)-mitoxantrone complex exhibits a higher lethality to Ehrlich ascites tumor cells than that of the free drag and shows stronger inh ibition ability on the DNA synthesis of the tumor cells. Thus the Ce(I V)-mitoxantrone complex may become a more potent antitumor drag than m itoxantrone. The different interaction model of mitoxantrone and its C e(IV) complex with DNA were studied by the methods of spectroscopy, el ectrochemistry, and electrophoresis. Ce(IV) ions chelate with oxygens of the hydroxyl groups at the 1,4 position and the carbonyl function o n C-9 and C-10, then intercalate into the base pairs of DNA together. The complexation of Ce(IV) gives rise to more compact binding of mitox antrone with DNA, and leads to an additional change on the normal conf ormation and the double-helical structure of DNA; this may be related to the more stronger action of the complex on DNA synthesis and surviv al of cultured tumor cells. (C) 1997 Elsevier Science Inc.