Oxidative stress modulates DNA methylation during melanocyte anchorage blockade associated with malignant transformation

Oxidative stress modulates DNA methylation during melanocyte anchorage blockade associated with malignant transformation

Author Campos, Ana Cristina Espindola Autor UNIFESP Google Scholar
Molognoni, Fernanda Autor UNIFESP Google Scholar
Melo, Fabiana Henrique Machado de Autor UNIFESP Google Scholar
Galdieri, Luciano de Camargo Autor UNIFESP Google Scholar
Carneiro, Celia Regina Whitaker Autor UNIFESP Google Scholar
D'Almeida, Vânia Autor UNIFESP Google Scholar
Correa, Mariangela Autor UNIFESP Google Scholar
Jasiulionis, Miriam Galvonas Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Both oxidative/nitrosative stress and alterations in DNA methylation are observed during carcinogenesis of different tumor types, but no clear correlation between these events has been demonstrated until now. Melanoma cell lines were previously established after submitting the nontumorigenic melanocyte lineage, melan-a, to cycles of anchorage blockade. in this work, increased intracellular oxidative species and nitric oxide levels, as well as alterations in the DNA methylation, were observed after melan-a detachment, which were also associated with a decrease in intracellular homocysteine (Hcy), an element in the methionine ( universal methyl donor) cycle. This alteration was accompanied by increase in glutathione (GSH) levels and methylated DNA content. Furthermore, a significant increase in dnmt1 and 3b expression was identified along melan-a anchorage blockade. (G)(L)-Nitro-L-arginine methyl esther ((L)-NAME), known as a nitric oxide synthase (NOS) inhibitor, and N-acetyl-(L)-cysteine (NAC) prevented the increase in global DNA methylation, as well as the increase in dnmt1 and 3b expression, observed during melan-a detachment. Interestingly, both (L)-NAME and NAC did not inhibit nitric oxide (NO) production in these cells, but abrogated superoxide anion production during anchorage blockade. in conclusion, oxidative stress observed during melanocyte anchorage blockade seems to modulate DNA methylation levels and may directly contribute to the acquisition of an anoikis-resistant phenotype through an epigenetic mechanism.
Keywords anoikis
carcinogenesis
epigenetics
DNA methylation
oxidative stress
Language English
Date 2007-12-01
Published in Neoplasia. Ann Arbor: Neoplasia Press, v. 9, n. 12, p. 1111-1121, 2007.
ISSN 1522-8002 (Sherpa/Romeo, impact factor)
Publisher Neoplasia Press
Extent 1111-1121
Origin http://dx.doi.org/10.1593/neo.07712
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000251446400013
URI http://repositorio.unifesp.br/handle/11600/30171

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