In vivo efficacy of a novel histone deacetylase inhibitor in combination with radiation for the treatment of gliomas.

Abstract

Histone modification has emerged as a promising approach to cancer therapy. We explored the in vivo efficacy of a butyric acid derivative, pivaloyloxymethyl butyrate (AN-9), for the treatment of gliomas. Relative to control and single-modality treatments, the combination of AN-9 and radiation significantly inhibited tumor growth and prolonged time to failure in mice bearing glioma xenografts. The enhanced response to radiation was accompanied by inhibition of cellular proliferation and by increased phosphorylation of H2AX, implicating DNA double-strand breaks in the antineoplastic effects of AN-9 and radiation. The data suggest that AN-9 in combination with radiation may be an effective therapy for malignant gliomas.

• Authors: Michal Entin-Meer, Xiaodong Yang, Scott R VandenBerg, Kathleen R Lamborn, Abraham Nudelman, Ada Rephaeli, Daphne Adele Haas-Kogan
• Journal: Neuro-oncology (Neuro Oncol) Vol. 9 Issue 2 Pg. 82-8 (Apr 2007) ISSN: 1522-8517 [Print] England
• PMID: 17347490 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Butyrates
• Enzyme Inhibitors
• Histone Deacetylase Inhibitors
• pivalyloxymethyl butyrate

Topics

• Animals
• Butyrates (therapeutic use)
• Cell Line, Tumor
• Combined Modality Therapy
• Dose-Response Relationship, Radiation
• Enzyme Inhibitors (therapeutic use)
• Glioma (drug therapy, radiotherapy)
• Histone Deacetylase Inhibitors
• Humans
• Mice
• Mice, Nude
• Transplantation, Heterologous