Induction of apoptosis in HL-60 cells by lithium

It has been established that lithium, a preferred drug for the treatment of manic depression, affects the growth of HL-60 cells. Concentrations of lithium above 10 mM were shown to be cytotoxic to these cells. However, the mechanism by which lithium induces its cytotoxicity is still obscure. In this study, we examined whether programmed cell death was involved in lithium cytotoxicity. Our findings show that lithium induced apoptosis in a time- and concentration-dependent manner. Morphological features and DNA fragmentation revealed that with 10 mM lithium, apoptosis was maximal at 72 hours of treatment. Interestingly, other monovalent ions were unable to elicit DNA fragmentation, suggesting that this phenomenon is specific for lithium. Cell cycle studies revealed that lithium arrested the cells at the G2/M phase.