Inhibition of proliferation and induction of apoptosis by melatonin in human myeloid HL-60 cells

Melatonin is an indoleamine that is synthesized in the pineal gland and has an extensive repertoire of biological activities. In the present study, we found that melatonin reduced the growth of the human myeloid leukemia cells HL-60, inhibiting progression from G₁ to S phase of the cell cycle and increasing apoptotic cell death. Furthermore, melatonin treatment elevated cytochrome c release from mitochondria and augmented caspase-3 and caspase-9 activities. Upregulation of Bax and downregulation of Bcl-2 was also observed upon melatonin treatment. The effects of melatonin were found not to be mediated by membrane receptors for the indoleamine. Together, our results suggest that melatonin reduces the viability of HL-60 cells via induction of apoptosis primarily through regulation of Bax/Bcl-2 expression.