Valproic acid modulates NCAM polysialylation and polysialyltransferase mRNA expression in human tumor cells.
Int Immunopharmacol
; 5(4): 757-69, 2005 Apr.
Article
em En
| MEDLINE
| ID: mdl-15710344
ABSTRACT
Polysialic acid (PSA) is a dynamically regulated carbohydrate modification of the neural cell adhesion molecule NCAM, which has been linked to cancer development and dissemination. Two enzymes, the polysialyltransferases ST8SiaIV and ST8SiaII, are known to be involved in the polysialylation of NCAM. The antiepileptic drug valproic acid (VPA) is associated with anti-cancer activity. In this study, VPA blocked the adhesion of several neuroectodermal tumor cell lines to human umbilical vein endothelial cells. Furthermore, VPA induced intracellular PSA accumulation and enhanced expression of PSA-NCAM on the cell surface. Using a semiquantitative RT-PCR strategy, VPA was shown to up-regulate ST8SiaIV mRNA, whereas ST8SiaII mRNA was down-regulated by this compound. Our data indicate that increased expression of ST8SiaIV enables accelerated polysialylation of NCAM, which might be coupled to a loss of adhesive functions of tumor cells.
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Base de dados:
MEDLINE
Assunto principal:
Ácidos Siálicos
/
Sialiltransferases
/
Ácido Valproico
/
Moléculas de Adesão de Célula Nervosa
/
Linhagem Celular Tumoral
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Alemanha