Melatonin induces mitochondrial-mediated apoptosis in human myeloid HL-60 cells

被引:132
作者
Bejarano, Ignacio
Redondo, Pedro C.
Espino, Javier
Rosado, Juan A.
Paredes, Sergio D.
Barriga, Carmen
Reiter, Russel J. [2 ]
Pariente, Jose A. [1 ]
Rodriguez, Ana B.
机构
[1] Univ Extremadura, Fac Sci, Dept Physiol, E-06071 Badajoz, Spain
[2] Univ Texas Hlth Sci, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA
关键词
apoptosis; caspases; HL-60; cells; melatonin; mitochondria; PERMEABILITY TRANSITION PORE; CANCER-CELLS; OXIDATIVE STRESS; CYTOCHROME-C; INHIBITION; ACTIVATION; PROLIFERATION; BAX; MECHANISMS; INDUCTION;
D O I
10.1111/j.1600-079X.2009.00675.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:392 / 400
页数:9
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