Effects of daunorubicin on cell growth, cell cycle and induction of apoptosis in HL-60 cells.

Administration of daunorubicin (DNR) at over 3.5 x 10(-8)M has been reported to block cells at G2 phase, but the precise mechanism of cell death induced by DNR is not well known. In this study effects of DNR at various concentrations on cell growth, cell cycle and induction of apoptosis in human leukemia cell line HL-60 cells were investigated. Administration of DNR at a high concentration (3.0 x 10(-8)M) inhibited cell growth to 3% as compared with untreated cells, blocked the cell cycle at G2 phase and induced cell-cycle non-specific apoptosis. Administration of DNR at a lower concentration (1.0 x 10(-8)M) inhibited cell growth to 77%, induced cell-cycle nonspecific apoptosis but did not produce G2 arrest. A longer duration of exposure to DNR was required to induce apoptosis by the lower concentration of DNR than by the higher concentration. These findings indicate that the effect of DNR on cell growth is caused by both G2 arrest and induction of apoptosis and that DNR induced apoptosis without G2 arrest. Moreover, continuous administration of a low concentration of DNR which has been considered to have no anticancer effect might be useful for treatment of leukemia and related diseases.