Teratogenic potency of valproate analogues evaluated by quantitative estimation of cellular morphology in vitro

Cell motility is inhibited by the antiepileptic compound, valproic acid and its teratogenic analogues

“…Previous reports have demonstrated that exposure to VPA in a number of cell lines causes dramatic changes in cell morphology in a dose and time dependent manner, the most prominent change being a strong increase in cell area [Berezin et al, 1996]. Although no straightforward relationship has been demonstrated between cell morphology and cell motility these results indicate that VPA might affect the latter parameter.…”

“…The effect of VPA on cell morphology has been shown not only for VPA, but also for VPA-analogues, the effect correlating with the teratogenic potency of the individual compounds [Berezin et al, 1996]. In order to examine whether the effect of VPA on cell motility might also be reproduced by VPA-analogues, and whether the effect might correlate to the teratogenic potency of the individual compounds, VPA and VPA-analogues with identical anticonvulsive effects but different teratogenic potencies were investigated for their effect on cell displacement.…”

“…We have recently demonstrated that treatment of cultured fibroblastoid mouse L-cells with VPA and selected VPA-analogues caused an increase in their mean cell area, the effects correlating to the teratogenic potency of the tested compounds [Berezin et al, 1996]. Although no straightforward relationship has been demonstrated between cell morphology and motility, these results indicate that VPA might be capable of modulating cellular motility, and that this effect might contribute to the teratogenic potency of the compound.…”

Protein kinase C inhibitors arrest the C6 glioma cell cycle at a mid-G1 phase restriction point: Implications for the antiproliferative action of valproate

“…This occurs in the early G I phase and eventually results in an accumulation of cells at the 5-6-hr time point at which they exhibit a differentiated phenotype (Berezin et al, 1996;Maguire and Regan, 1991;. At this point a significant decrease in total PKC activity is observed.…”

“…This antiproliferative action occurs at a defined restriction point in the G I phase at which cells assurne a differentiated phenotype as judged by altered morphology, gene expression and cell substratum adhesivity (Berezin et al, 1996;. This antiproliferative effect becomes apparent in the early GI phase (Martin and Regan, 1991), during which VPA may perturb signal transduction events leading to the eventual accumulation of cells at the mid-G 1 restriction point.…”