Korean J Physiol Pharmacol.  2010 Dec;14(6):365-369. 10.4196/kjpp.2010.14.6.365.

Melatonin Induces Apoptotic Cell Death via p53 in LNCaP Cells

• Kim CH
• Yoo YM

• KMID: 2071707
• DOI: http://doi.org/10.4196/kjpp.2010.14.6.365

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.

Keyword

Melatonin; p53; p38; JNK; LNCaP cells

MeSH Terms

Anthracenes
Apoptosis
Caspase 3
Caspase 8
Caspase 9
Cell Death
Flavonoids
Imidazoles
Melatonin
Poly(ADP-ribose) Polymerases
Prostate
Protein Kinases
Pyridines
Anthracenes
Caspase 3
Caspase 8
Caspase 9
Flavonoids
Imidazoles
Melatonin
Poly(ADP-ribose) Polymerases
Protein Kinases
Pyridines