Pirarubicin plus Cu(II) induces oxidative DNA damage similarly to doxorubicin, suggesting a common mechanism for the antitumor effects of anthracyclines.
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Supports shared anthracycline mechanisms in models; leaves open human efficacy or toxicity relevance.
Background/Aim: One mechanism of the anticancer action of anthracyclines is believed to be oxidative DNA damage. Previously, we reported that doxorubicin induced oxidative DNA damage in the presence of Cu(II). However, the mechanism of pirarubicin-induced oxidative DNA damage has not been well clarified. Materials and Methods: DNA damage by pirarubicin in the presence of Cu(II) was analyzed using pBR322 plasmid DNA. O2•− derived from pirarubicin in the presence of Cu(II) was detected by cytochrome c reduction. Results: Pirarubicin induced DNA damage in the presence of Cu(II). Scavenger experiments suggest that reactive species are generated from H2O2 and Cu(I). Pirarubicin induced O2•− production in the presence of Cu(II). Conclusion: These findings suggest that pirarubicin plus Cu(II) induces oxidative DNA damage in a similar manner to doxorubicin, and Cu(II)-mediated oxidative DNA damage may serve as a common mechanism for antitumor effects of anthracyclines.
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Mizutani et al. (2018) studied this question.
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