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Cancer Cell International
Published in: Cancer Cell International 1/2006

Open Access 01-12-2006 | Primary research

Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines

Authors: Alma Chavez-Blanco, Carlos Perez-Plasencia, Enrique Perez-Cardenas, Claudia Carrasco-Legleu, Edgar Rangel-Lopez, Blanca Segura-Pacheco, Lucia Taja-Chayeb, Catalina Trejo-Becerril, Aurora Gonzalez-Fierro, Myrna Candelaria, Gustavo Cabrera, Alfonso Duenas-Gonzalez

Published in: Cancer Cell International | Issue 1/2006

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Abstract

Background

Among the epigenetic alterations occurring in cancer, DNA hypermethylation and histone hypoacetylation are the focus of intense research because their pharmacological inhibition has shown to produce antineoplastic activity in a variety of experimental models. The objective of this study was to evaluate the combined antineoplastic effect of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in a panel of cancer cell lines.

Results

Hydralazine showed no growth inhibitory effect on cervical, colon, breast, sarcoma, glioma, and head & neck cancer cell lines when used alone. On the contrary, valproic acid showed a strong growth inhibitory effect that is potentiated by hydralazine in some cell lines. Individually, hydralazine and valproic acid displayed distinctive effects upon global gene over-expression but the number of genes over-expressed increased when cells were treated with the combination. Treatment of HeLa cells with hydralazine and valproic acid lead to an increase in the cytotoxicity of gemcitabine, cisplatin and adriamycin. A higher antitumor effect of adriamycin was observed in mice xenografted with human fibrosarcoma cells when the animals were co-treated with hydralazine and valproic acid.

Conclusion

Hydralazine and valproic acid, two widely used drugs for cardiovascular and neurological conditions respectively have promising antineoplastic effects when used concurrently and may increase the antitumor efficacy of current cytotoxic agents.
Appendix
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Metadata
Title
Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines
Authors
Alma Chavez-Blanco
Carlos Perez-Plasencia
Enrique Perez-Cardenas
Claudia Carrasco-Legleu
Edgar Rangel-Lopez
Blanca Segura-Pacheco
Lucia Taja-Chayeb
Catalina Trejo-Becerril
Aurora Gonzalez-Fierro
Myrna Candelaria
Gustavo Cabrera
Alfonso Duenas-Gonzalez
Publication date
01-12-2006
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2006
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-6-2

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