- Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma.
Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma.
Nature medicine (2014-11-18)
Rintaro Hashizume, Noemi Andor, Yuichiro Ihara, Robin Lerner, Haiyun Gan, Xiaoyue Chen, Dong Fang, Xi Huang, Maxwell W Tom, Vy Ngo, David Solomon, Sabine Mueller, Pamela L Paris, Zhiguo Zhang, Claudia Petritsch, Nalin Gupta, Todd A Waldman, C David James
PMID25401693
ABSTRACT
Pediatric brainstem gliomas often harbor oncogenic K27M mutation of histone H3.3. Here we show that GSKJ4 pharmacologic inhibition of K27 demethylase JMJD3 increases cellular H3K27 methylation in K27M tumor cells and demonstrate potent antitumor activity both in vitro against K27M cells and in vivo against K27M xenografts. Our results demonstrate that increasing H3K27 methylation by inhibiting K27 demethylase is a valid therapeutic strategy for treating K27M-expressing brainstem glioma.
MATERIALS
Product Number
Brand
Product Description
Sigma-Aldrich
ApopTag Peroxidase In Situ Apoptosis Detection Kit, The ApopTag Peroxidase In Situ Apoptosis Detection Kit detects apoptotic cells in situ by labeling & detecting DNA strand breaks by the TUNEL method.
Sigma-Aldrich
Anti-Histone H3.3 Antibody, K27M mutant, from rabbit, purified by affinity chromatography
Sigma-Aldrich
SF7761 Human DIPG H3.3-K27M Cell Line, SF7761 pediatric diffuse intrinsic pontine glioma (DIPG) cell line harbors the histone H3.3 Lys 27-to-methionine (K27M) mutation and can support research and drug development efforts targeting DIPG.