Toxicity of daunorubicin and naphthoquinones to HL-60 cells: an involvement of oxidative stress.
Incubation of HL-60 cells with anthracycline daunorubicin caused an appearance of viable apoptotic, nonviable apoptotic, necrotic (nonviable nonapoptotic) and chromatin-free (late apoptotic) cells. Both necrotic and apoptotic cell responses were partly prevented by antioxidant N,N'-diphenyl-p-phenylene diamine (DPPD) and iron-chelating agent, desferrioxamine, suggesting an involvement of activated oxygen species. The comparison of cytotoxicity of daunorubicin and of 5-hydroxy- and 5,8-dihydroxy-1,4-naphthoquinones revealed that at equitoxic concentrations, hydroxynaphthoquinones induced a larger number of necrotic cells in comparison to daunorubicin, a process being partly prevented by DPPD and desferrioxamine. However, we have found that cytotoxicity of daunorubicin was markedly higher in comparison with a series of naphtho- and benzoquinones, where an increase of cytotoxicity upon increase in single-electron reduction potential of quinones (E(1)7) was observed, pointing out to redox cycling as to the main factor of cytotoxicity. This discrepancy could be explained by additional factor(s) of daunorubicin cytotoxicity, e.g., DNA-intercalation, or selective accumulation of daunorubicin in cell nucleus.
Dickancaite
E
E
Institute of Biochemistry, Vilnius, Lithuania.
Cenas
N
N
Kalvelyte
A
A
Serapiniene
N
N
D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000633:toxicity*; D003676:Deferoxamine / Q000494:pharmacology; D018922:HL-60 Cells / Q000187:drug effects*; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology; D009285:Naphthoquinones / Q000633:toxicity*; D018384:Oxidative Stress / Q000502:physiology*; D010655:Phenylenediamines / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D016227:Benzoquinones; D007502:Iron Chelating Agents; D009285:Naphthoquinones; D010655:Phenylenediamines; C004845:N,N'-diphenyl-4-phenylenediamine; D003676:Deferoxamine; D003630:Daunorubicin