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Published on: July 17, 2018
Melatonin induces mitochondrial-mediated apoptosis in human myeloid HL-60 cells
Ignacio Bejarano1, Pedro C Redondo, Javier Espino
1Department of Physiology, University of Extremadura, Badajoz, Spain.
Abstract:
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.
Insights
Melatonin, a hormone, can trigger apoptosis (programmed cell death) in human leukemia cells (HL-60). This study shows melatonin activates key caspases and proapoptotic proteins, suggesting oncostatic effects.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Melatonin's role in apoptosis is complex, showing antiapoptotic effects in normal cells but potentially proapoptotic effects in certain tumor cells.
- Understanding melatonin's impact on cancer cell death is crucial for exploring therapeutic strategies.
Purpose of the Study:
- To investigate the effect of melatonin on apoptosis in the human leukemia cell line HL-60.
- To elucidate the molecular mechanisms underlying melatonin-induced apoptosis in these cells.
Main Methods:
- HL-60 cells were treated with melatonin (1 mM).
- Assays were performed to measure caspase-3 and -9 activities, mitochondrial membrane potential, and cell death.
- Expression and association of proapoptotic proteins Bax and Bid were analyzed.
Main Results:
- Melatonin significantly increased caspase-3 and -9 activities in a time-dependent manner.
- Mitochondrial membrane depolarization and permeability transition pore induction were observed.
- Melatonin treatment led to increased cell death (apoptosis/necrosis) and elevated levels/association of Bax and Bid proteins.
Conclusions:
- Melatonin exhibits proapoptotic effects in the human myeloid leukemia cell line HL-60.
- The findings suggest potential oncostatic roles for melatonin in this leukemia model.
- Melatonin induces apoptosis via caspase activation, mitochondrial dysfunction, and modulation of Bax/Bid pathways.
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