title: Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unidad de Investigación Biomédica en Cancer. Instituto de Investigaciones Biomédicas, UNAM, /Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Alma
authors.initials: A
authors.lastname: Chavez-Blanco
authors.affiliation: Unidad de Investigación Biomédica en Cancer. Instituto de Investigaciones Biomédicas, UNAM, /Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Perez-Plasencia
authors.affiliation: Unidad de Investigación Biomédica en Cancer. Instituto de Investigaciones Biomédicas, UNAM, /Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Enrique
authors.initials: E
authors.lastname: Perez-Cardenas
authors.affiliation: Unidad de Investigación Biomédica en Cancer. Instituto de Investigaciones Biomédicas, UNAM, /Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Claudia
authors.initials: C
authors.lastname: Carrasco-Legleu
authors.affiliation: Unidad de Investigación Biomédica en Cancer. Instituto de Investigaciones Biomédicas, UNAM, /Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Edgar
authors.initials: E
authors.lastname: Rangel-Lopez
authors.affiliation: Unidad de Investigación Biomédica en Cancer. Instituto de Investigaciones Biomédicas, UNAM, /Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Blanca
authors.initials: B
authors.lastname: Segura-Pacheco
authors.affiliation: Unidad de Investigación Biomédica en Cancer. Instituto de Investigaciones Biomédicas, UNAM, /Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Lucia
authors.initials: L
authors.lastname: Taja-Chayeb
authors.affiliation: Unidad de Investigación Biomédica en Cancer. Instituto de Investigaciones Biomédicas, UNAM, /Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Catalina
authors.initials: C
authors.lastname: Trejo-Becerril
authors.affiliation: Unidad de Investigación Biomédica en Cancer. Instituto de Investigaciones Biomédicas, UNAM, /Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Aurora
authors.initials: A
authors.lastname: Gonzalez-Fierro
authors.affiliation: Division of Clinical Research, Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Myrna
authors.initials: M
authors.lastname: Candelaria
authors.affiliation: Unidad de Investigación Biomédica en Cancer. Instituto de Investigaciones Biomédicas, UNAM, /Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Cabrera
authors.affiliation: Unidad de Investigación Biomédica en Cancer. Instituto de Investigaciones Biomédicas, UNAM, /Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Duenas-Gonzalez