Anti-neoplastic properties of hydralazine in prostate cancer

• DOI: 10.18632/oncotarget.1909
• Publication Date: 2015-09-15T23:39:14Z
• Authors: Inês Graça; Elsa J Sousa; Pedro Costa-Pinheiro; Filipa Q Vieira; Jorge Torres-Ferr...; Maria Gabriela Ma...; Rui Henrique; Carmen Jerónimo
• Keywords: DU145; Hydralazine; DNMT1

Prostate cancer (PCa) is a major cause of cancer-related morbidity and mortality worldwide. Although early disease often efficiently managed therapeutically, available options for advanced are mostly ineffective. Aberrant DNA methylation associated with gene-silencing genes common feature PCa. Therefore, inhibitors might constitute an attractive alternative therapy. Herein, we evaluated the anti-cancer properties hydralazine, non-nucleoside methyltransferases (DNMT) inhibitor, in PCa cell lines. In vitro assays showed that hydralazine exposure led to significant dose time dependent growth inhibition, increased apoptotic rate decreased invasiveness. Furthermore, it also induced cycle arrest damage. These phenotypic effects were particularly prominent DU145 cells. Following exposure, levels DNMT1, DNMT3a DNMT3b mRNA DNMT1 protein depicted. Moreover, decrease GSTP1, BCL2 CCND2 promoter levels, concomitant transcript re-expression, was observed. Interestingly, restored androgen receptor expression, upregulation its target p21 line. Protein array analysis suggested blockage EGF signaling pathway likely be main mechanism action Our data demonstrate attenuated malignant phenotype cells, useful therapeutic tool.