The cytotoxic effects of 5-OH-1,4-naphthoquinone and 5,8-diOH-1,4-naphthoquinone on doxorubicin-resistant human leukemia cells (HL-60).
The effect of 5-OH-1,4-naphthoquinone and 5,8-diOH-1,4-naphthoquinone, two quinones highly reactive with oxygen, was studied on HL-60 and HL-60R cells. The multidrug resistance developed by the doxorubicin-resistant HL-60 cell line did not prevent the cytotoxic effect of these compounds, at clinically relevant concentrations. An increase in cellular defenses against oxygen radicals seemed to be one of the features developed by HL-60R, since the homogenate from this cell line had only 65% of the ability of the original cell line to form oxygen radicals during doxorubicin reduction. This result may be explained in part by the slight increase in superoxide dismutase and DT-diaphorase enzymatic activities.
Segura-Aguilar
J
J
Department of Biochemistry, Wallenberg Laboratory, University of Stockholm, Sweden.
Jönsson
K
K
Tidefelt
U
U
Paul
C
C
D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001711:Biotransformation; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005609:Free Radicals; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009285:Naphthoquinones / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D013482:Superoxide Dismutase / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D005609:Free Radicals; D009285:Naphthoquinones; C005503:naphthazarin; D004317:Doxorubicin; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); D010100:Oxygen; C005134:juglone