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 drug and shows stronger inhibition ability on the DNA synthesis of the tumor cells. Thus the Ce(IV)-mitoxantrone complex may become a more potent antitumor drug than mitoxantrone. The different interaction model of mitoxantrone and its Ce(IV) complex with DNA were studied by the methods of spectroscopy, electrochemistry, and electrophoresis. Ce(IV) ions chelate with oxygens of the hydroxyl groups at the 1,4 position and the carbonyl function on 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 mitoxantrone with DNA, and leads to an additional change on the normal conformation and the double-helical structure of DNA; this may be related to the more stronger action of the complex on DNA synthesis and survival of cultured tumor cells.
Wang
H
H
State Key Laboratory of Coordination Chemistry, Nanjing University, People's Republic of China.
Yang
P
P
Tian
Y
Y
Zhang
Z
Z
Zhao
C
C
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002563:Cerium / Q000494:pharmacology*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004563:Electrochemistry; D004586:Electrophoresis / Q000379:methods; D051379:Mice; D008942:Mitoxantrone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D013053:Spectrophotometry / Q000379:methods; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
C108978:(mitoxantrone)cerium(IV); D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D009942:Organometallic Compounds; D002563:Cerium; D004247:DNA; D008942:Mitoxantrone; D013936:Thymidine