Fas/Fas ligand regulation mediates cell death in human Ewing's sarcoma cells treated with melatonin.

Abstract:

BACKGROUND:Despite recent advances in cancer therapy, the 5-year survival rate for Ewing's sarcoma is still very low, and new therapeutic approaches are necessary. It was found previously that melatonin induces cell death in the Ewing's sarcoma cell line, SK-N-MC, by activating the extrinsic apoptotic pathway. METHODS:Melatonin actions were analysed by metabolic viability/survival cell assays, flow cytometry, quantitative PCR for mRNA expression, western blot for protein activation/expression and electrophoretic mobility shift assay for transcription factor activation. RESULTS:Melatonin increases the expression of Fas and its ligand Fas L, this increase being responsible for cell death induced by the indolamine. Melatonin also produces a transient increase in intracellular oxidants and activation of the redox-regulated transcription factor Nuclear factor-kappaB. Inhibition of such activation prevents cell death and Fas/Fas L upregulation. Cytotoxic effect and Fas/Fas L regulation occur in all Ewing's cell lines studied, and do not occur in the other tumour cell lines studied where melatonin does not induce cell death. CONCLUSION:Our data offers new insights in the study of alternative therapeutic strategies in the treatment of Ewing's sarcoma. Further attention deserves to be given to the differences in the cellular biology of sensitive tumours that could explain the cytotoxic effect of melatonin and the increase in the level of free radicals caused by this molecule, in particular cancer types.

journal_name

Br J Cancer

authors

García-Santos G,Martin V,Rodríguez-Blanco J,Herrera F,Casado-Zapico S,Sánchez-Sánchez AM,Antolín I,Rodríguez C

doi

10.1038/bjc.2012.66

subject

Has Abstract

pub_date

2012-03-27 00:00:00

pages

1288-96

issue

7

eissn

0007-0920

issn

1532-1827

pii

bjc201266

journal_volume

106

pub_type

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