Effects of a novel synthetic retinoid on malignant glioma in vitro: inhibition of cell proliferation, induction of apoptosis and differentiation.
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.
INSERM U-421, Faculté de médicine, 8 rue du Général Sarrail, 94010 cedex, Créteil, France.
S L
SL
Costa
E
E
Paillaud
C
C
Fages
C
C
Rochette-Egly
J L
JL
Plassat
H
H
Jouault
A
A
Perzelova
M
M
Tardy
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002471:Cell Transformation, Neoplastic; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D012176:Retinoids / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C099555:CD 437; D012176:Retinoids