Melatonin Induces Apoptotic Cell Death via p53 in LNCaP Cells
The Korean Journal of Physiology and Pharmacology
;
: 365-369, 2010.
Article
in English
| WPRIM
| ID: wpr-728358
ABSTRACT
In this study, we examined whether melatonin promotes apoptotic cell death via p53 in prostate LNCaP cells. Melatonin treatment significantly curtailed the growth of LNCaP cells in a dose- and time-dependent manner. Melatonin treatment (0 to 3 mM) induced the fragmentation of poly(ADP-ribose) polymerase (PARP) and activation of caspase-3, caspase-8, and caspase-9. Moreover, melatonin markedly activated Bax expression and decreased Bcl-2 expression in dose increments. To investigate p53 and p21 expression, LNCaP cells were treated with 0 to 3 mM melatonin. Melatonin increased the expressions of p53, p21, and p27. Treatment with mitogen-activated protein kinase (MAPK) inhibitors, PD98059 (ERK inhibitor), SP600125 (JNK inhibitor) and SB202190 (p38 inhibitor), confirmed that the melatonin-induced apoptosis was p21-dependent, but ERK-independent. With the co-treatment of PD98059 and melatonin, the expression of p-p53, p21, and MDM2 did not decrease. These effects were opposite to the expression of p-p53, p21, and MDM2 observed with SP600125 and SB202190 treatments. Together, these results suggest that p53-dependent induction of JNK/p38 MAPK directly participates in apoptosis induced by melatonin.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Prostate
/
Protein Kinases
/
Pyridines
/
Flavonoids
/
Cell Death
/
Poly(ADP-ribose) Polymerases
/
Apoptosis
/
Caspase 3
/
Caspase 8
/
Caspase 9
Language:
English
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
2010
Type:
Article
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