Document Detail

Melatonin induces apoptosis in human neuroblastoma cancer cells.
MedLine Citation:
PMID:  16879318     Owner:  NLM     Status:  MEDLINE    
Low concentrations (nanomolar) of melatonin had been previously shown to inhibit cell proliferation in several cancer cell lines as well as in experimental animal models. Additionally, cell growth inhibition and differentiation of prostate cancer cell lines by high concentrations (micromolar to millimolar) of melatonin have been recently reported. In the present paper, we show the induction of apoptosis by high doses of melatonin in the human neuroblastoma cell line SK-N-MC. We found accumulation of cells in the G2/M cell cycle phase and induction of cellular death, measured as lactate dehydrogenase (LDH) released into the culture medium, under millimolar concentration of melatonin. Apoptosis was evaluated using 4,6-diamidino-2-phenylindole staining, DNA gel electrophoresis, electron microscopy, and annexin V binding. Apoptosis progressed through the classical pathway, which involves caspase-3 activation. Cell death was dose and time-dependent; the lowest effective concentration of melatonin was 100 microm. Treatment with 1 mm melatonin for 6 days induced cell death in 75% of the cells. This novel finding shows that a nontoxic natural indoleamine may be potential therapy for some types of human neuroblastomas.
Guillermo García-Santos; Isaac Antolín; Federico Herrera; Vanesa Martín; Jezabel Rodriguez-Blanco; Maria del Pilar Carrera; Carmen Rodriguez
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of pineal research     Volume:  41     ISSN:  0742-3098     ISO Abbreviation:  J. Pineal Res.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-01     Completed Date:  2006-09-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8504412     Medline TA:  J Pineal Res     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  130-5     Citation Subset:  IM    
Departamento de Morfología y Biología Celular, Facultad de Medicina de la Universidad de Oviedo, Oviedo, Spain.
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MeSH Terms
Apoptosis / drug effects*
Caspase 3
Caspases / metabolism
Cell Cycle / drug effects
Cell Line, Tumor
DNA Fragmentation
Dose-Response Relationship, Drug
L-Lactate Dehydrogenase / metabolism
Melatonin / administration & dosage,  pharmacology*
Signal Transduction
Reg. No./Substance:
73-31-4/Melatonin; EC Dehydrogenase; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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