Effects of a novel synthetic retinoid on malignant glioma in vitro: inhibition of cell proliferation, induction of apoptosis and differentiation

Autor: E. Paillaud, J.L. Plassat, A Perzelova, C. Rochette-Egly, Marcienne Tardy, C. Fages, H Jouault, Silvia Lima Costa
Rok vydání: 2001
Předmět:
Zdroj: European Journal of Cancer. 37:520-530
ISSN: 0959-8049
DOI: 10.1016/s0959-8049(00)00430-5
Popis: Among six synthetic retinoids tested, the retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) was highly efficient in inducing growth inhibition of 8MG-BA and GL-15 human glioblastoma cell lines, with growth arrest at the S phase of the cell cycle. CD 437 also induced apoptosis in these cells, with 8MG-BA being the most sensitive. In these cells, induction of apoptosis by CD437 has been related to the downregulation of Bcl-2 expression and to CPP32 activation, but not to p53 expression. The remaining non-apoptotic cells presented a morphological pattern of astroglial differentiation with overexpression of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS). The mechanism of action of CD437, originally developed as a RARgamma agonist, is not yet elucidated. However, our results suggest that it acts through an increase of the expression of retinoid-inducible genes, such as RARbeta2 and/or RARalpha2.
Databáze: OpenAIRE