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

Deubzer, Hedwig E. and Ehemann, Volker and Kulozik, Andreas E. and Westermann, Frank and Savelyeva, Larissa and Kopp-Schneider, Annette and Riester, Daniel and Schwab, Manfred and Witt, Olaf (2008) Anti-neuroblastoma activity of Helminthosporium carbonum (HC)-toxin is superior to that of other differentiating compounds in vitro. CANCER LETTERS, 264 (1). pp. 21-28. ISSN 0304-3835

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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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Item Type:Article
Uncontrolled Keywords:HC-toxin; retinoids; N-myc; E2F-1; RB tumor suppressor network
Subjects:Biomedical Science > Nanomedicine
ID Code:588
Deposited By:M T V
Deposited On:11 Dec 2008 14:59
Last Modified:11 Dec 2008 14:59

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