Effects of Tiron, 4,5-dihydroxy-1,3-benzene disulfonic acid, on human promyelotic HL-60 leukemia cell differentiation and death

Tiron, 4,5-dihydroxy-1,3-benzene disulfonic acid, has been known to be a widely used antioxidant to rescue ROS-evoked cell death and a non-toxic chelator to alleviate an acute metal overload. In this study, we showed that Tiron is a potent inducer of cell differentiation and apoptotic cell death in human promyelotic HL-60 leukemia cell. At a low level of concentration (0.5 mM) induced severe DNA damage in HL-60 cells, as measured by the cytokinesis-block micronucleus test and the comet assay. Consequently, high dose of Tiron led to apoptotic cell death, which showed the DNA fragmentation, the caspase activation and the unbalance between antiapoptotic (Bcl-2) and proapoptotic proteins (Bax). However, an exogenous supplement of iron (FeCl 3) reversed all of these effects, the cell differentiation and the apoptotic cell death. Therefore, these results suggest that Tiron-mediated differentiation and cell death result from the disturbance of iron metabolism.