Inhibitory effects of epigenetic modulators and differentiation inducers on human medulloblastoma cell lines

Background: medulloblastoma (mb) is the most common malignant brain tumor in childhood with a 5-year survival of approximately 60%. we have recently shown that treatment of human mb cells with 5-aza-2'-deoxycytidine (5-aza-dc) reduces the clonogenic survival significantly. here,we tested combinatorial effects of 5-aza-dc with other epigenetic (valproic acid,saha) and differentiation- inducing drugs (resveratrol,abacavir,retinoic acid) on human mb cells in vitro to intensify the antitumor therapy further. methods. three human mb cell lines were treated with 5-aza-dc alone or in combination for three or six days. metabolic activity was measured by wst-1 assay. to determine long-term reproductive survival,clonogenic assays were performed. induction of dna double-strand break (dsb) repair was measured by γh2ax assay. results: the applied single drugs,except for atra,reduced the metabolic activity dose-dependently in all mb cell lines. longer treatment times enhanced the reduction of metabolic activity by 5-aza-dc. combinatorial treatments showed differential,cell line-dependent responses indicating an important impact of the genetic background. 5-aza-dc together with resveratrol was found to exert the most significant inhibitory effects on metabolic activity in all cell lines. 5-aza-dc alone reduced the clonogenicity of mb cells significantly and induced dsb with no further changes after adjuvant administration of resveratrol. conclusion: the observed significant decrease in metabolic activity by combinatorial treatment of mb cells with 5-aza-dc and resveratrol does not translate into long-term reproductive survival deficiency in vitro. further studies in animal models are needed to clarify the resveratrol-mediated anticancer mechanisms in vivo. © 2013 patties et al.; licensee biomed central ltd.