Melatonin induces mitochondrial-mediated apoptosis in human myeloid HL-60 cells.
The role of melatonin in the mediation of apoptotic events has recently gained attention, especially after recent studies have reported that melatonin exerts antiapoptotic actions in normal cells but may activate proapoptotic pathways in some tumor cells. Here, we have evaluated the effect of melatonin on apoptosis in the human leukemia cell line HL-60. Melatonin treatment (1 mm) induced a significant increase in caspase-3 and -9 activities. The effect of melatonin on the activation of caspases was time dependent, reaching a maximum after 12 hr of stimulation, and then decreasing to a minimum after 72 hr. Treatment with melatonin also evoked mitochondrial membrane depolarization and permeability transition pore induction, which caused loss of mitochondrial staining by calcein, and increased cell death by apoptosis/necrosis as demonstrated by propidium iodide positive-staining of cells after 72 hr of stimulation. In addition, the exposure of cells to melatonin resulted in an activation and association of the proapoptotic proteins Bax and Bid, as well as promoting detectable increases in the expression of both proteins. We conclude that melatonin has proapoptotic and/or oncostatic effects in the human myeloid cell line HL-60.
Bejarano
Ignacio
I
Department of Physiology, University of Extremadura, Badajoz, Spain.
Redondo
Pedro C
PC
Espino
Javier
J
Rosado
Juan A
JA
Paredes
Sergio D
SD
Barriga
Carmen
C
Reiter
Russel J
RJ
Pariente
José A
JA
Rodríguez
Ana B
AB
D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle; D005452:Fluoresceins / Q000378:metabolism; D005453:Fluorescence; D018922:HL-60 Cells; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D005452:Fluoresceins; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053453:Caspase 9; D008550:Melatonin; C007740:fluorexon