Histone acetyltransferase inhibitors block neuroblastoma cell growth in vivo View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-02

AUTHORS

J M Gajer, S D Furdas, A Gründer, M Gothwal, U Heinicke, K Keller, F Colland, S Fulda, H L Pahl, I Fichtner, W Sippl, M Jung

ABSTRACT

We have previously described novel histone acetyltransferase (HAT) inhibitors that block neuroblastoma cell growth in vitro. Here we show that two selected pyridoisothiazolone HAT inhibitors, PU139 and PU141, induce cellular histone hypoacetylation and inhibit growth of several neoplastic cell lines originating from different tissues. Broader in vitro selectivity profiling shows that PU139 blocks the HATs Gcn5, p300/CBP-associated factor (PCAF), CREB (cAMP response element-binding) protein (CBP) and p300, whereas PU141 is selective toward CBP and p300. The pan-inhibitor PU139 triggers caspase-independent cell death in cell culture. Both inhibitors block growth of SK-N-SH neuroblastoma xenografts in mice and the PU139 was shown to synergize with doxorubicin in vivo. The latter also reduces histone lysine acetylation in vivo at concentrations that block neoplastic xenograft growth. This is one of the very few reports on hypoacetylating agents with in vivo anticancer activity. More... »

PAGES

e137

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/oncsis.2014.51

DOI

http://dx.doi.org/10.1038/oncsis.2014.51

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1004757525

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25664930


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