Melatonin Induces Apoptotic Cell Death via p53 in LNCaP Cells.
10.4196/kjpp.2010.14.6.365
- Author:
Chi Hyun KIM
1
;
Yeong Min YOO
Author Information
1. Department of Biomedical Engineering, College of Health Science, Yonsei University, Wonju 220-710, Korea. yooym@yonsei.ac.kr
- Publication Type:Original Article
- Keywords:
Melatonin;
p53;
p38;
JNK;
LNCaP cells
- MeSH:
Anthracenes;
Apoptosis;
Caspase 3;
Caspase 8;
Caspase 9;
Cell Death;
Flavonoids;
Imidazoles;
Melatonin;
Poly(ADP-ribose) Polymerases;
Prostate;
Protein Kinases;
Pyridines
- From:The Korean Journal of Physiology and Pharmacology
2010;14(6):365-369
- CountryRepublic of Korea
- Language:English
-
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.
