Hydralazine target: From blood vessels to the epigenome
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BioMed Central
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Hydralazine target: From blood vessels to the epigenome Claudia Arce2, Blanca Segura-Pacheco1, Enrique Perez-Cardenas1, Lucia TajaChayeb1, Myrna Candelaria2 and Alfonso Dueñnas-Gonzalez*1 Address: 1Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas (IIB)/Instituto Nacional de Cancerología, Universidad Nacional Autónoma de Mexico, Mexico City, Mexico and 2Division of Clinical Research, Instituto Nacional de Cancerología, Mexico City, Mexico Email: Claudia Arce - [email protected]; Blanca Segura-Pacheco - [email protected]; Enrique PerezCardenas - [email protected]; Lucia Taja-Chayeb - [email protected]; Myrna Candelaria - [email protected]; Alfonso DueñnasGonzalez* - [email protected] * Corresponding author
Published: 28 February 2006 Journal of Translational Medicine2006, 4:10
doi:10.1186/1479-5876-4-10
Received: 22 December 2005 Accepted: 28 February 2006
This article is available from: http://www.translational-medicine.com/content/4/1/10 © 2006Arce et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Hydralazine was one of the first orally active antihypertensive drugs developed. Currently, it is used principally to treat pregnancy-associated hypertension. Hydralazine causes two types of side effects. The first type is an extension of the pharmacologic effect of the drug and includes headache, nausea, flushing, hypotension, palpitation, tachycardia, dizziness, and salt retention. The second type of side effects is caused by immunologic reactions, of which the drug-induced lupuslike syndrome is the most common, and provides clues to underscoring hydralazine's DNA demethylating property in connection with studies demonstrating the participation of DNA methylation disorders in immune diseases. Abnormalities in DNA methylation have long been associated with cancer. Despite the fact that malignant tumors show global DNA hypomethylation, regional hypermethylation as a means to silence tumor suppressor gene expression has attracted the greatest attention. Reversibility of methylation-induced gene silencing by pharmacologic means, which in turns leads to antitumor effects in experimental and clinical scenarios, has directed efforts toward developing clinically useful demethylating agents. Among these, the most widely used comprise the nucleosides 5-azacytidine and 2'deoxy-5azacytidine; however, these agents, like current cytotoxic chemotherapy, causes myelosuppression among other side effects that could limit exploitation of their demethylating properties. Among non-nucleoside DNA demethylating drugs currently under development, the oral drug hydralazine possess the ability to reactivate tumor suppressor gene expression, which is silenced by promoter hypermethyl
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