Document Detail

Valproic acid increases the in vitro effects of nitrosureas on human glioma cell lines.
MedLine Citation:
PMID:  18196869     Owner:  NLM     Status:  MEDLINE    
Valproic acid (VPA) has been recently investigated for its anticancer properties in different tumors, including malignant gliomas. The aim of the present work was to evaluate the effects of VPA, alone or in combination with other chemotherapeutic drugs, on in vitro growth of human glioma cell lines. A172, U373, U138, U87, and SW1783 were treated with VPA alone or in combination with mitoxantrone, etoposide, or 1,3-bis(2-chloroethyl)-l-nitrosourea (BCNU). The effects of treatments on cell growth were assessed with crystal violet staining and analyzed using the combination index (CI). The percentage of apoptotic cells and the DNA content for cell cycle phases detection were also investigated by flow cytometry. Despite a certain variability, glioma cell lines were rather resistant to the drugs tested. Addition of VPA decreased the IC50 of the chemotherapeutic agents in all cell lines tested. This effect was more evident with BCNU. The synergic effect of the association of VPA and BCNU was related to an increased block of cell cycle with accumulation in S-G2/M phases of cell cycle rather than an increased programmed cell death. In our experimental model, VPA showed anticancer properties per se on human glioma cell lines and our data support the hypothesis that, if used in association with conventional chemotherapy, it might improve the effects of single chemotherapeutic agents.
Emilio Ciusani; Marco Balzarotti; Chiara Calatozzolo; Ugo de Grazia; Amerigo Boiardi; Andrea Salmaggi; Danilo Croci
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncology research     Volume:  16     ISSN:  0965-0407     ISO Abbreviation:  Oncol. Res.     Publication Date:  2007  
Date Detail:
Created Date:  2008-01-16     Completed Date:  2008-03-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9208097     Medline TA:  Oncol Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  453-63     Citation Subset:  IM    
Department of Clinical Investigation, Neurological National Institute Carlo Besta, Milan, Italy.
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MeSH Terms
Acetylation / drug effects
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Apoptosis / drug effects
Astrocytoma / drug therapy*,  metabolism,  pathology
Carmustine / administration & dosage,  pharmacology*
Cell Cycle / drug effects
Cell Growth Processes / drug effects
Cell Line, Tumor
Drug Synergism
Etoposide / administration & dosage
Glioblastoma / drug therapy*,  metabolism,  pathology
Mitoxantrone / administration & dosage
Valproic Acid / administration & dosage,  pharmacology*
Reg. No./Substance:
154-93-8/Carmustine; 33419-42-0/Etoposide; 65271-80-9/Mitoxantrone; 99-66-1/Valproic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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