Abstract:
:Histone modification has emerged as a promising approach to cancer therapy. We explored the efficacy of a novel class of histone deacetylase inhibitors in the treatment of malignant gliomas. Treatment of glioma cell lines with two butyric acid derivatives, pivaloylomethyl butyrate (AN-9) and butyroyloxymethyl butyrate (AN-1), induced hyperacetylation, increased p21(Cip1) expression, inhibited proliferation, and enhanced apoptosis. Histone deacetylase inhibitor-induced apoptosis was mediated primarily by caspase-8. Treatment of cells with AN-1 or AN-9 for 24 hours before exposure to gamma-irradiation potentiated further caspase-8 activity and resultant apoptosis. Clonogenic survival curves revealed marked reductions in cell renewal capacity of U251 MG cells exposed to combinations of AN-1 and radiation. Preliminary in vivo experiments using human glioma cell lines grown as xenografts in mouse flanks suggest in vivo efficacy of AN-9. The data suggest that novel butyric acid prodrugs provide a promising treatment strategy for malignant gliomas as single agents and in combination with radiation therapy.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Entin-Meer M,Rephaeli A,Yang X,Nudelman A,VandenBerg SR,Haas-Kogan DAdoi
10.1158/1535-7163.MCT-05-0087keywords:
subject
Has Abstractpub_date
2005-12-01 00:00:00pages
1952-61issue
12eissn
1535-7163issn
1538-8514pii
4/12/1952journal_volume
4pub_type
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