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Histone deacetylase inhibitors and cell death

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Abstract

Histone deacetylases (HDACs) are a vast family of enzymes involved in chromatin remodeling and have crucial roles in numerous biological processes, largely through their repressive influence on transcription. In addition to modifying histones, HDACs also target many other non-histone protein substrates to regulate gene expression. Recently, HDACs have gained growing attention as HDAC-inhibiting compounds are being developed as promising cancer therapeutics. Histone deacetylase inhibitors (HDACi) have been shown to induce differentiation, cell cycle arrest, apoptosis, autophagy and necrosis in a variety of transformed cell lines. In this review, we mainly discuss how HDACi may elicit a therapeutic response to human cancers through different cell death pathways, in particular, apoptosis and autophagy.

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Acknowledgments

We thank all Zhong laboratory members for suggestions. The author apologizes to all colleagues whose work may not have been cited for space reasons. Thanks Rhea Sumpter, Mary Grace Lin and Tabitha Ting for critical reading of the manuscript. The work in our lab is supported by grants to Q. Z. from the Welch Foundation, the new investigator award from the Ellison Medical foundation, American Cancer Society Research Scholar Grant (RSG-11-274-01-CCG) and NIH R01 (CA133228).

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  1. Department of Internal Medicine, Center for Autophagy Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Room Y9206C, Dallas, TX, 75390-9113, USA

    Jing Zhang & Qing Zhong

  2. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Jing Zhang & Qing Zhong

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Zhang, J., Zhong, Q. Histone deacetylase inhibitors and cell death. Cell. Mol. Life Sci. 71, 3885–3901 (2014). https://doi.org/10.1007/s00018-014-1656-6

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