SODIUM VALPROATE INHIBITS IN-VIVO GROWTH OF HUMAN NEUROBLASTOMA-CELLS

Sodium valproate (VPA) belongs to the group of simple branched-chain f atty acids and due its anticonvulsive activity is broadly applied in t he treatment of epilepsy. We previously showed that VPA is able to ind uce cellular differentiation, to enhance immunogenicity and to inhibit proliferation of human neuroblastoma (NB) cells in vitro. Furthermore , we demonstrated that VPA inhibits proliferation, enhances neural cel l adhesion molecule expression and decreases CD44 expression of human and rat glioma cells in vitro. In the present study we investigated th e antitumoral effects of VPA on established human NB xenografts from U KF-NB-3 human NB cells in athymic (nude) mice. When the animals develo ped s.c. tumors of about 100 mm(3) volume they were treated with 400 o r 200 mg/kg/day VPA i.p. At the end of the treatment period (40 days) tumor volumes in animals treated with 400 and 200 mg/kg VPA were about 4- (p<0.0001) and 2-fold (p<0.0005) smaller than in the saline-treate d control group, respectively. Histological examination of the remnant tumors of treated animals revealed induction of differentiation by in duction of stroma-rich tumors and nodules that contained elongated NB cells. Pyknotic nuclei and apoptotic bodies indicated induction of apo ptosis. We conclude that VPA is able to abrogate NB growth in vivo and may therefore be useful in the treatment of NB patients.