Mizutani Hideki, Nishimoto Ayano, Hotta Saki, Ikemura Kenji, Imai Masanori, Miyazawa Daisuke, Ohta Kinya, Ikeda Yoshiaki, Maeda Tohru, Yoshikawa Masae, Hiraku Yusuke, Kawanishi Shosuke
College of Pharmacy, Kinjo Gakuin University, Nagoya, Japan
College of Pharmacy, Kinjo Gakuin University, Nagoya, Japan.
Anticancer Res. 2018 May;38(5):2643-2648. doi: 10.21873/anticanres.12506.
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.
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.
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).
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.
背景/目的：蒽环类药物抗癌作用的一种机制被认为是氧化DNA损伤。此前，我们报道了阿霉素在铜（II）存在的情况下会诱导氧化DNA损伤。然而，吡柔比星诱导氧化DNA损伤的机制尚未得到充分阐明。
使用pBR322质粒DNA分析吡柔比星在铜（II）存在时对DNA的损伤。通过细胞色素c还原检测铜（II）存在时吡柔比星产生的氧。
吡柔比星在铜（II）存在时诱导DNA损伤。清除剂实验表明活性物质由羟基自由基和铜（I）产生。吡柔比星在铜（II）存在时诱导氧的产生。
这些发现表明吡柔比星加铜（II）以与阿霉素相似的方式诱导氧化DNA损伤，并且铜（II）介导的氧化DNA损伤可能是蒽环类药物抗肿瘤作用的共同机制。
