Oxidative DNA Damage Induced by Pirarubicin, an Anthracycline Anticancer Agent, in the Presence of Copper(II).

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. O 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 HO and Cu(I). Pirarubicin induced O 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.