Maltol/iron-mediated apoptosis in HL60 cells: Participation of reactive oxygen species

Apoptosis of HL60 cells by maltol was analyzed in relation to the maltol/iron-mediated generation of reactive oxygen species. Addition of maltol with FeSO4 induced an apoptotic cell death as judged by flow cytometry analysis and DNA fragmentation on electrophoresis, but maltol or iron alone did not affect the cells. Treatment of HL60 cells with maltol/iron complex caused an effective inactivation of aconitase the most sensitive enzyme to reactive oxygen species. Maltol/iron-mediated apoptosis and the inactivation of aconitase was prevented by TEMPOL, the scavenger of reactive oxygen species. These findings suggest that maltol/iron complex can generate reactive oxygen species by the redox cycling, resulting in an apoptosis of HL60 cells. Cytotoxicity of maltol can be explained by the prooxidant properties of this compound.