Targeting histone demethylases in MYC-driven neuroblastomas with ciclopirox

Jun Yang, Sandra Milasta, Dongli Hu, Alaa M. AlTahan, Rodrigo B. Interiano, Junfang Zhou, Jesse Davidson, Jonathan Low, Wenwei Lin, Ju Bao, Pollyanna Goh, Amit C. Nathwani, Ruoning Wang, Yingdi Wang, Su Sien Ong, Vincent A. Boyd, Brandon Young, Sourav Das, Anang Shelat, Yinan WuZhenmei Li, Jie J. Zheng, Ashutosh Mishra, Yong Cheng, Chunxu Qu, Junmin Peng, Douglas R. Green, Stephen White, R. Kiplin Guy, Taosheng Chen, Andrew M. Davidoff

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4626-4638
Number of pages13
JournalCancer Research
Volume77
Issue number17
DOIs
StatePublished - Sep 1 2017

Fingerprint

ciclopirox
Histone Demethylases
Neuroblastoma
Antifungal Agents
Oxidative Phosphorylation
Epigenomics
Neoplasms
Cell Survival
Transcription Factors

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Yang, J., Milasta, S., Hu, D., AlTahan, A. M., Interiano, R. B., Zhou, J., ... Davidoff, A. M. (2017). Targeting histone demethylases in MYC-driven neuroblastomas with ciclopirox. Cancer Research, 77(17), 4626-4638. https://doi.org/10.1158/0008-5472.CAN-16-0826

Targeting histone demethylases in MYC-driven neuroblastomas with ciclopirox. / Yang, Jun; Milasta, Sandra; Hu, Dongli; AlTahan, Alaa M.; Interiano, Rodrigo B.; Zhou, Junfang; Davidson, Jesse; Low, Jonathan; Lin, Wenwei; Bao, Ju; Goh, Pollyanna; Nathwani, Amit C.; Wang, Ruoning; Wang, Yingdi; Ong, Su Sien; Boyd, Vincent A.; Young, Brandon; Das, Sourav; Shelat, Anang; Wu, Yinan; Li, Zhenmei; Zheng, Jie J.; Mishra, Ashutosh; Cheng, Yong; Qu, Chunxu; Peng, Junmin; Green, Douglas R.; White, Stephen; Guy, R. Kiplin; Chen, Taosheng; Davidoff, Andrew M.

In: Cancer Research, Vol. 77, No. 17, 01.09.2017, p. 4626-4638.

Research output: Contribution to journalArticle

Yang, J, Milasta, S, Hu, D, AlTahan, AM, Interiano, RB, Zhou, J, Davidson, J, Low, J, Lin, W, Bao, J, Goh, P, Nathwani, AC, Wang, R, Wang, Y, Ong, SS, Boyd, VA, Young, B, Das, S, Shelat, A, Wu, Y, Li, Z, Zheng, JJ, Mishra, A, Cheng, Y, Qu, C, Peng, J, Green, DR, White, S, Guy, RK, Chen, T & Davidoff, AM 2017, 'Targeting histone demethylases in MYC-driven neuroblastomas with ciclopirox', Cancer Research, vol. 77, no. 17, pp. 4626-4638. https://doi.org/10.1158/0008-5472.CAN-16-0826
Yang J, Milasta S, Hu D, AlTahan AM, Interiano RB, Zhou J et al. Targeting histone demethylases in MYC-driven neuroblastomas with ciclopirox. Cancer Research. 2017 Sep 1;77(17):4626-4638. https://doi.org/10.1158/0008-5472.CAN-16-0826
Yang, Jun ; Milasta, Sandra ; Hu, Dongli ; AlTahan, Alaa M. ; Interiano, Rodrigo B. ; Zhou, Junfang ; Davidson, Jesse ; Low, Jonathan ; Lin, Wenwei ; Bao, Ju ; Goh, Pollyanna ; Nathwani, Amit C. ; Wang, Ruoning ; Wang, Yingdi ; Ong, Su Sien ; Boyd, Vincent A. ; Young, Brandon ; Das, Sourav ; Shelat, Anang ; Wu, Yinan ; Li, Zhenmei ; Zheng, Jie J. ; Mishra, Ashutosh ; Cheng, Yong ; Qu, Chunxu ; Peng, Junmin ; Green, Douglas R. ; White, Stephen ; Guy, R. Kiplin ; Chen, Taosheng ; Davidoff, Andrew M. / Targeting histone demethylases in MYC-driven neuroblastomas with ciclopirox. In: Cancer Research. 2017 ; Vol. 77, No. 17. pp. 4626-4638.
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AU - Interiano, Rodrigo B.

AU - Zhou, Junfang

AU - Davidson, Jesse

AU - Low, Jonathan

AU - Lin, Wenwei

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AU - Goh, Pollyanna

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AU - Li, Zhenmei

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AU - Mishra, Ashutosh

AU - Cheng, Yong

AU - Qu, Chunxu

AU - Peng, Junmin

AU - Green, Douglas R.

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