Idarubicin and idarubicinol are less affected by topoisomerase II-related multidrug resistance than is daunorubicin.
We investigated the cytotoxicity and cellular pharmacology of idarubicin (IDA), idarubicinol (IDAol) and daunorubicin (DNR) in K562/VP-H2 cells, which show topoisomerase II-related multidrug resistance but do not overexpress P-glycoprotein. K562/VP-H2 cells were less resistant to IDA and IDAol than to DNR. There was no significant difference in the accumulation of each drug between K562 and K562/VP-H2 cells. The cleavage of DNA induced by each drug was decreased in K562/VP-H2 cells, however, the decrease in cleavage in K562/VP-H2 cells was less with IDA and IDAol than with DNR. These results suggest that IDA and IDAol have more cytotoxic potency than DNR in topoisomerase II-related multidrug-resistant leukemia cells.
Fukushima
T
T
First Department of Internal Medicine, Fukui Medical University, Matsuoka, Japan.
Inoue
H
H
Takemura
H
H
Kishi
S
S
Yamauchi
T
T
Inai
K
K
Nakayama
T
T
Imamura
S
S
Urasaki
Y
Y
Nakamura
T
T
Ueda
T
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002457:Cell Extracts / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000494:pharmacology; D004250:DNA Topoisomerases, Type II / Q000502:physiology*; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015255:Idarubicin / Q000032:analysis / Q000494:pharmacology*; D014343:Trypan Blue; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
D000970:Antineoplastic Agents; D002457:Cell Extracts; D003603:Cytotoxins; C054440:idarubicinol; D004250:DNA Topoisomerases, Type II; D014343:Trypan Blue; D015255:Idarubicin; D003630:Daunorubicin