| Literature DB >> 28684529 |
Jun Yang1, Sandra Milasta2, Dongli Hu3, Alaa M AlTahan3, Rodrigo B Interiano3, Junfang Zhou3, Jesse Davidson3, Jonathan Low4, Wenwei Lin4, Ju Bao5, Pollyanna Goh6, Amit C Nathwani6, Ruoning Wang7, Yingdi Wang8, Su Sien Ong4, Vincent A Boyd4, Brandon Young4, Sourav Das4, Anang Shelat4, Yinan Wu5, Zhenmei Li5, Jie J Zheng5, Ashutosh Mishra9, Yong Cheng10, Chunxu Qu11, Junmin Peng9, Douglas R Green2, Stephen White5, R Kiplin Guy4, Taosheng Chen4, Andrew M Davidoff3.
Abstract
Histone lysine demethylases facilitate the activity of oncogenic transcription factors, including possibly MYC. Here we show that multiple histone demethylases influence the viability and poor prognosis of neuroblastoma cells, where MYC is often overexpressed. We also identified the approved small-molecule antifungal agent ciclopirox as a novel pan-histone demethylase inhibitor. Ciclopirox targeted several histone demethylases, including KDM4B implicated in MYC function. Accordingly, ciclopirox inhibited Myc signaling in parallel with mitochondrial oxidative phosphorylation, resulting in suppression of neuroblastoma cell viability and inhibition of tumor growth associated with an induction of differentiation. Our findings provide new insights into epigenetic regulation of MYC function and suggest a novel pharmacologic basis to target histone demethylases as an indirect MYC-targeting approach for cancer therapy. Cancer Res; 77(17); 4626-38. ©2017 AACR. ©2017 American Association for Cancer Research.Entities:
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Year: 2017 PMID： 28684529 PMCID： PMC5581701 DOI： 10.1158/0008-5472.CAN-16-0826
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701