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Anti-neuroblastoma activity of Helminthosporium carbonum (HC)-toxin is superior to that of other differentiating compounds in vitro

Item Type:Article
Title:Anti-neuroblastoma activity of Helminthosporium carbonum (HC)-toxin is superior to that of other differentiating compounds in vitro
Creators Name:Deubzer, H.E. and Ehemann, V. and Kulozik, A.E. and Westermann, F. and Savelyeva, L. and Kopp-Schneider, A. and Riester, D. and Schwab, M. and Witt, O.
Abstract:Treatment of high-risk neuroblastoma (NB) is difficult. Novel therapeutics improving survival rates are urgently required. We have previously shown that the histone deacetylase inhibitor (HDACI) Helminthosporium carbonum (HC)-toxin induces differentiation of neuroblastoma (NB) cells. Here, we show that HC-toxin inhibits the growth of both established NB cell lines and primary cultures with and without amplified MYCN stronger than retinoids (RAs) and other HDACIs (MS-275, n-butyric acid, suberoylanilide hydroxamic acid, trichostatin A, valproic acid). Nanomolar dosages suppress E2F-1, N-myc, Skp2, Mad2 and survivin proteins, found at high levels in high-risk NBs, more efficiently than both RAs and other HDACIs. The level of hypophosphorylated active retinoblastoma (RB) tumor suppressor protein is increased most effectively. HC-toxin's epoxy group is essential for inhibiting HDACs and promoting anti-NB activity. Without this functional group, those cellular effects are not observed. In conclusion, the anti-NB activity of HC-toxin is superior to that of RAs and that of all other HDACIs tested.
Keywords:HC-Toxin, Retinoids, N-Myc, E2F-1, RB Tumor Suppressor Network
Source:Cancer Letters
ISSN:0304-3835
Publisher:Elsevier (Ireland)
Volume:264
Number:1
Page Range:21-28
Date:8 June 2008
Official Publication:https://doi.org/10.1016/j.canlet.2008.01.002
PubMed:View item in PubMed

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