Superior cytotoxic potency of mitoxantrone in interaction with DNA: comparison with that of daunorubicin.
The mechanism of action of the anthraquinone antileukemic drug mitoxantrone (MIT) was investigated and compared with that of daunorubicin (DNR) with emphasis on the interaction with DNA to clarify the more potent cytotoxic activity of MIT than DNR in human leukemia cells. MIT showed similar characteristics to those of the anthracyclines such as DNR in that binding of MIT to DNA was associated with reduced template activity and cleavage of DNA in HL-60 human leukemia cells. However, as compared with DNR, MIT showed an increased number of binding sites on DNA, a lower inhibition constant for DNA polymerization, and a greater DNA cleavage activity. These properties may contribute to its greater potency than that of DNR, with which MIT inhibited the proliferation of HL-60 human leukemia cells.
Fukushima
T
T
First Department of Internal Medicine, Fukui Medical School, Matsuoka, Japan.
Kawai
Y
Y
Nakayama
T
T
Yamauchi
T
T
Yoshida
A
A
Urasaki
Y
Y
Imamura
S
S
Kamiya
K
K
Tsutani
H
H
Ueda
T
T
Nakamura
T
T
D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000187:drug effects; D003630:Daunorubicin / Q000378:metabolism* / Q000494:pharmacology; D016521:Electrophoresis, Gel, Pulsed-Field; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008942:Mitoxantrone / Q000378:metabolism* / Q000494:pharmacology
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D008942:Mitoxantrone; D004259:DNA-Directed DNA Polymerase; D003630:Daunorubicin