Cytotoxicity and DNA damage caused by 4-demethoxydaunorubicin and its metabolite 4-demethoxy-13-hydroxydaunorubicin in human acute myeloid leukemia cells.
4-Demethoxydaunorubicin (4-DMDR) and its major metabolite 4-demethoxy-13-hydroxydaunorubicin (4-DMDRol) were investigated for their cytotoxicity and mode of action against human leukemic cells. The drug and its metabolite appeared to be equally potent as both inhibitors of cell proliferation and inducers of DNA double-strand breaks in the OCI AML-3 cell line and cells derived directly from patients with acute myeloid leukemia (AML). This suggests that 4-DMDRol plays an important role in the antileukemic activity of 4-DMDR.
Instituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
M
M
Limonta
A
A
Biondi
G
G
Giudici
G
G
Specchia
C
C
Catapano
G
G
Masera
T
T
Barbui
M
M
D'Incalci
D000328:Adult; D000970:Antineoplastic Agents; D002455:Cell Division / Q000187:drug effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects*; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D015255:Idarubicin / Q000378:metabolism / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; C054440:idarubicinol; D015255:Idarubicin; D003630:Daunorubicin