Idarubicin, an Anthracycline, Induces Oxidative DNA Damage in the Presence of Copper (II)

  title={Idarubicin, an Anthracycline, Induces Oxidative DNA Damage in the Presence of Copper (II)},
  author={Hideki Mizutani and Chiaki Shiga and Masanori Imai and Kenji Ikemura and Yuki Kitamura and Kin-ya Ohta and Daisuke Miyazawa and Mayuko Sakanashi and Tomoko Tahira and Tohru Maeda and Yusuke Hiraku and Shosuke Kawanishi},
  journal={AntiCancer Research},
  pages={5399 - 5404}
Background/Aim: The aim of the present study was to investigate whether idarubicin (IDR) induces oxidative DNA damage in the presence of copper (II). Materials and Methods: DNA damage was evaluated by pBR322 plasmid DNA cleavage. The formation of oxidative stress markers [O2•− and 8-hydroxy-2’-deoxyguanosine (8-OHdG)] was analysed. Results: IDR induced DNA damage and O2•− and 8-OHdG generation in the presence of copper (II). Conclusion: IDR induced oxidative DNA damage in the presence of copper… Expand

Figures from this paper

Oxidative Stress in Cancer Cell Metabolism
An overview of the generation and sources of ROS within tumor cells, ROS-associated signaling pathways, their regulation by antioxidant defense systems, as well as the effect of elevated ROS production in tumor progression is provided. Expand


Oxidative DNA Damage Induced by Pirarubicin, an Anthracycline Anticancer Agent, in the Presence of Copper(II).
Findings suggest that pirarubicin plus Cu(II) induces oxidative DNA damage in a similar manner to doxorubic in, and Cu( II)-mediated oxidative DNADamage may serve as a common mechanism for antitumor effects of anthracyclines. Expand
Oxidative DNA Damage and Apoptosis Induced by Aclarubicin, an Anthracycline: Role of Hydrogen Peroxide and Copper
ACR-induced DNA damage and apoptosis can be accounted for by the involvement of H2O2 and Cu(I). Expand
Oxidative DNA damage induced by a hydroperoxide derivative of cyclophosphamide.
Investigation of DNA damage in a human leukemia cell line and its H(2)O(2)-resistant clone HP100 concludes that, in addition to DNA cross-linking, oxidative DNA damage through H( 2)O (2) generation may participate in the anti-tumor effects of 4-HC. Expand
Redox cycling of Cu(II) by 6-mercaptopurine leads to ROS generation and DNA breakage: possible mechanism of anticancer activity
Since 6MP possesses DNA damaging ability by producing reactive oxygen species (ROS) in the presence of Cu(II), it may also possess apoptosis-inducing activity by involving endogenous copper ions, which would be an alternative and copper-dependent pathway for anticancer activity of 6MP. Expand
Mechanism of UVA-dependent DNA Damage Induced by An Antitumor Drug Dacarbazine in Relation to its Photogenotoxicity
Photoactivated DTIC generates the carbene and aryl radicals, which may induce both DNA adduct and 8-oxodG formation, resulting in photogenotoxicity, which could provide an insight into the safe usage of DTIC. Expand
Bioreduction of idarubicin and formation of ROS responsible for DNA cleavage by NADPH-cytochrome P450 reductase and its potential role in the antitumor effect.
  • Haydar Çelik, E. Arinç
  • Chemistry, Medicine
  • Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
  • 2008
Investigation of the possible involvement of NADPH-cytochrome P450 reductase in the bioreductive activation of idarubicin to DNA-damaging species suggested that DNA damage by idarUBicin occurs through a mechanism which involves its redox cycling with P450 reduction to generate reactive oxygen species (ROS). Expand
Mechanism of apoptosis induced by doxorubicin through the generation of hydrogen peroxide.
The mechanism of apoptosis induced by DOX in the human leukemia cell line HL-60 and the H(2)O(2)-resistant sub-clone, HP100 was investigated, suggesting that the critical apoptotic trigger of DOX is considered to be oxidative DNA damage by the DOX-induced direct H( 2)O (2) generation, although DOx-induced apoptosis may involve topoisomerase II inhibition. Expand
Molecular mechanisms of DNA damage induced by procarbazine in the presence of Cu(II).
In addition to alkylation, oxidative DNA damage may play important roles in not only antitumor effects but also mutagenesis and carcinogenesis induced by procarbazine. Expand
DNA damage induced by NADPH cytochrome P450 reductase-activated idarubicin in sensitive and multidrug resistant MCF7 breast cancer cells.
The obtained results suggest that CPR-activation of IDA does not significantly change the cellular DNA damage response of studied sensitive MCF7 and multidrug resistant MCF 7/DOX500 breast cancer cells, even if the results concerning the interaction of IDa undergoing CPR activation with naked DNA showed the important differences in comparison with the drug alone (non-activated). Expand
Metal-mediated oxidative DNA damage induced by methylene blue.
It is suggested that metal-mediated DNA damage contributes to MB-mediated carcinogenesis through redox reaction by UV-visible spectrometry. Expand