Pirarubicin, an Anthracycline Anticancer Agent, Induces Apoptosis Through Generation of Hydrogen Peroxide

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.

Keywords: Pirarubicin; ROS; apoptosis; hydrogen peroxide.