Oxidative DNA Damage and Apoptosis Induced by Aclarubicin, an Anthracycline: Role of Hydrogen Peroxide and Copper

• Published in: Anticancer research Vol. 39; no. 7; pp. 3443 - 3451
• Main Authors: Mizutani, Hideki, Hayashi, Yuka, Hashimoto, Miyabi, Imai, Masanori, Ichimaru, Yoshimi, Kitamura, Yuki, Ikemura, Kenji, Miyazawa, Daisuke, Ohta, Kinya, Ikeda, Yoshiaki, Maeda, Tohru, Yoshikawa, Masae, Hiraku, Yusuke, Kawanishi, Shosuke
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.07.2019
• Subjects: Aclarubicin - adverse effects; Anthracycline; Antibiotics, Antineoplastic - adverse effects; Apoptosis; Apoptosis - drug effects; Caspase; Caspase-3; Cell Line, Tumor; Copper; Copper - pharmacology; Deoxyribonucleic acid; DNA; DNA Damage; Fluorescent indicators; Humans; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Leukemia; Neoplasms - metabolism; Plasmids; apoptosis; copper; Aclarubicin; DNA damage; ROS; hydrogen peroxide
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.13490

This study aimed to investigate aclarubicin (ACR)-induced oxidative DNA damage and apoptosis. ACR-induced apoptosis was analyzed using HL-60 leukemia cells and HP100 cells, hydrogen peroxide (H O )-resistant cells derived from HL-60 cells. ACR-induced DNA damage was analyzed using plasmid DNA. HL-60 cells were more sensitive to ACR than HP100 cells. In HP100 cells, DNA ladder formation and caspase-3/7 activity induced by ACR were suppressed or delayed in comparison to those in HL-60 cells. ACR-induced DNA damage occurred in the presence of Cu(II), and scavenger experiments showed that the reactive species causing DNA damage appeared to be generated from H O and Cu(I). Moreover, we detected intracellular Cu(I) induced by ACR in HL-60 cells, using CopperGREEN™, a fluorescent probe for detection of Cu(I) ion specifically. ACR-induced DNA damage and apoptosis can be accounted for by the involvement of H O and Cu(I).