Antitumor activity of sodium valproate in cultures of human neuroblastoma cells.
Valproic acid (VPA) is a simple branched-chain fatty acid that has anticonvulsant activity and is widely used in the treatment of epilepsy. VPA was found to effect growth and differentiation of human neuroblastoma (NB) cells in vitro at concentrations that have been achieved in humans with no significant adverse effects. Treatment of UKF-NB-2 and UKF-NB-3 NB cell lines with VPA at concentrations ranging from 0.5 to 2 mM resulted in neuronal morphological differentiation characterized by extension of cellular processes without significant effects on cell viability. Ultrastructural features of VPA-treated cells were consistent with the neuronal type of differentiation. VPA treatment of NB cells was associated with decreased expression of N-myc oncoprotein and increased expression of neural cell adhesion molecule in their membrane. Treatment of NB cells with 0.5 mM VPA increased their sensitivity to lymphokine-activated killer lysis. The results indicate that VPA, at non-toxic pharmacological concentrations, arrests the growth, induces differentiation and increases immunogenicity of NB cells through non-toxic mechanisms.
Cinatl
J
J
Zentrum der Hygiene, Abteilung Medizinische Virologie, Zentrum der Kinderheilkunde und Jugendmedizin, Frankfurt, Germany.
Cinatl
J
J
Scholz
M
M
Driever
P H
PH
Henrich
D
D
Kabickova
H
H
Vogel
J U
JU
Doerr
H W
HW
Kornhuber
B
B
D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008854:Microscopy, Electron; D009363:Neoplasm Proteins / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009447:Neuroblastoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D019006:Neural Cell Adhesion Molecules; D016271:Proto-Oncogene Proteins c-myc; D014635:Valproic Acid