In vivo efficacy of a novel histone deacetylase inhibitor in combination with radiation for the treatment of gliomas.
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.
Entin-Meer
Michal
M
Department of Radiation Oncology, Neurological Surgery, and Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA. memeer@cc.ucsf.edu
Yang
Xiaodong
X
VandenBerg
Scott R
SR
Lamborn
Kathleen R
KR
Nudelman
Abraham
A
Rephaeli
Ada
A
Haas-Kogan
Daphne Adele
DA
D000818:Animals; D002087:Butyrates / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D014183:Transplantation, Heterologous
D002087:Butyrates; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; C070441:pivalyloxymethyl butyrate