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Valproic Acid Increases the In Vitro Effects of Nitrosureas on Human Glioma Cell Lines

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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)-1-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.

Keywords: Apoptosis; BCNU; Cell cycle; Glioma; Histone deacetylase; Valproic acid

Document Type: Research Article


Affiliations: 1: Department of Clinical Investigation, Neurological National Institute “Carlo Besta,” Milan, Italy 2: Department of Neurology, Neurological National Institute “Carlo Besta,” Milan, Italy

Publication date: October 1, 2007

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  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.

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