> Merkliste Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
Medientyp: E-Artikel Titel: Histone deacetylase inhibitor Helminthosporium carbonum (HC)‐toxin suppresses the malignant phenotype of neuroblastoma cells Beteiligte: Deubzer, Hedwig E.; Ehemann, Volker; Westermann, Frank; Heinrich, Ralf; Mechtersheimer, Gunhild; Kulozik, Andreas E.; Schwab, Manfred; Witt, Olaf Erschienen: Wiley, 2008 Erschienen in: International Journal of Cancer, 122 (2008) 8, Seite 1891-1900 Sprache: Englisch DOI: 10.1002/ijc.23295 ISSN: 1097-0215; 0020-7136 Entstehung: Anmerkungen: Beschreibung: AbstractThe survival rate of children with advanced neuroblastoma (NB) is dismal despite intensive multimodal therapy. The limited efficacy and the frequent and serious side effects of currently used therapeutic regimens necessitate the development of new, less toxic treatment strategies. This study shows that the histone deacetylase inhibitor Helminthosporium carbonum (HC)‐toxin suppresses the malignant phenotype of both established NB cell lines and primary NB cells with and without amplified MYCN at dosages lower than 20 nM. HC‐toxin induces cell cycle arrest and apoptosis as well as neuronal differentiation and diminishes both colony formation and invasive growth. These cellular changes are accompanied by the transcriptional repression of cell cycle regulators of the retinoblastoma (RB) tumor suppressor network found at high levels in NBs with poor prognosis, like E2F‐1 and its targets Skp2, N‐myc, Mad2 and survivin. The levels of the hypophosphorylated active form of RB, and of cyclin‐dependent kinase inhibitors including p15INK4b, p16INK4a, p21cip1/waf‐1 and p27kip1 are increased. In conclusion, nanomolar doses of the HDACI HC‐toxin cause a shift to a differentiated and benign phenotype of NB cells that is associated with an activation of the RB tumor suppressor network. © 2007 Wiley‐Liss, Inc. Zugangsstatus: Freier Zugang