Hideki Mizutani1, Saki Hotta2, Ayano Nishimoto2, Kenji Ikemura2,3, Daisuke Miyazawa2, Yoshiaki Ikeda2, Tohru Maeda2, Masae Yoshikawa2, Yusuke Hiraku4, Shosuke Kawanishi5. 1. College of Pharmacy, Kinjo Gakuin University, Nagoya, Japan mizu@kinjo-u.ac.jp kawanisi@suzuka-u.ac.jp. 2. College of Pharmacy, Kinjo Gakuin University, Nagoya, Japan. 3. Department of Pharmacy, Mie University Hospital, Tsu, Japan. 4. Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Japan. 5. Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Japan mizu@kinjo-u.ac.jp kawanisi@suzuka-u.ac.jp.
Abstract
BACKGROUND/AIM: Pirarubicin (THP) has shown equal or superior cytotoxicity compared to doxorubicin. One of the main anticancer actions of doxorubicin is believed to be involved in ROS (reactive oxygen species) generation. Therefore, the anticancer mechanisms of THP may involve ROS generation. The aim of this study was to clarify the mechanisms of THP-induced apoptosis through ROS generation. MATERIALS AND METHODS: We analyzed the apoptotic events induced by THP in HL-60 cells and HP100 cells, hydrogen peroxide (H2O2)-resistant cells derived from HL-60. RESULTS: The apparent cytotoxicity could be detected at above 0.1 μM in HL-60 cells after 24-h incubation, whereas it was suppressed under these conditions in HP100 cells. In HP100 cells, THP-induced apoptosis, evaluated by DNA ladder formation, H2O2 generation, mitochondrial membrane potential decrease and caspase-3/7 activity, was suppressed or delayed compared to those of HL-60 cells. CONCLUSION: These findings can be explained by the involvement of H2O2 generation in the THP apoptotic pathway. This is the first report on THP-induced apoptosis through the H2O2 generation. Copyright
BACKGROUND/AIM: Pirarubicin (THP) has shown equal or superior cytotoxicity compared to doxorubicin. One of the main anticancer actions of doxorubicin is believed to be involved in ROS (reactive oxygen species) generation. Therefore, the anticancer mechanisms of THP may involve ROS generation. The aim of this study was to clarify the mechanisms of THP-induced apoptosis through ROS generation. MATERIALS AND METHODS: We analyzed the apoptotic events induced by THP in HL-60 cells and HP100 cells, hydrogen peroxide (H2O2)-resistant cells derived from HL-60. RESULTS: The apparent cytotoxicity could be detected at above 0.1 μM in HL-60 cells after 24-h incubation, whereas it was suppressed under these conditions in HP100 cells. In HP100 cells, THP-induced apoptosis, evaluated by DNA ladder formation, H2O2 generation, mitochondrial membrane potential decrease and caspase-3/7 activity, was suppressed or delayed compared to those of HL-60 cells. CONCLUSION: These findings can be explained by the involvement of H2O2 generation in the THP apoptotic pathway. This is the first report on THP-induced apoptosis through the H2O2 generation. Copyright