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Patra S, Praharaj PP, Klionsky DJ, et al. Vorinostat in autophagic cell death: A critical insight into autophagy-mediated, -associated and -dependent cell death for cancer prevention. Drug Discov Today. 2021;27(1):269-279doi: 10.1016/j.drudis.2021.08.004.
Patra, S., Praharaj, P. P., Klionsky, D. J., & Bhutia, S. K. (2022). Vorinostat in autophagic cell death: A critical insight into autophagy-mediated, -associated and -dependent cell death for cancer prevention. Drug discovery today, 27(1), 269-279. https://doi.org/10.1016/j.drudis.2021.08.004
Patra, Srimanta, et al. "Vorinostat in autophagic cell death: A critical insight into autophagy-mediated, -associated and -dependent cell death for cancer prevention." Drug discovery today vol. 27,1 (2022): 269-279. doi: https://doi.org/10.1016/j.drudis.2021.08.004
Patra S, Praharaj PP, Klionsky DJ, Bhutia SK. Vorinostat in autophagic cell death: A critical insight into autophagy-mediated, -associated and -dependent cell death for cancer prevention. Drug Discov Today. 2022 Jan;27(1):269-279. doi: 10.1016/j.drudis.2021.08.004. Epub 2021 Aug 13. PMID: 34400351; PMCID: PMC8714665.
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Drug Discov Today. 2022 Jan;27(1):269-279. doi: 10.1016/j.drudis.2021.08.004. Epub 2021 Aug 13.

Vorinostat in autophagic cell death: A critical insight into autophagy-mediated, -associated and -dependent cell death for cancer prevention.

Drug discovery today

Srimanta Patra, Prakash P Praharaj, Daniel J Klionsky, Sujit K Bhutia

Affiliations

  1. Cancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, Rourkela 769008, Odisha, India.
  2. Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
  3. Cancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, Rourkela 769008, Odisha, India. Electronic address: [email protected].

PMID: 34400351 PMCID: PMC8714665 DOI: 10.1016/j.drudis.2021.08.004

Abstract

Histone deacetylases (HDACs) inhibit the acetylation of crucial autophagy genes, thereby deregulating autophagy and autophagic cell death (ACD) and facilitating cancer cell survival. Vorinostat, a broad-spectrum pan-HDAC inhibitor, inhibits the deacetylation of key autophagic markers and thus interferes with ACD. Vorinostat-regulated ACD can have an autophagy-mediated, -associated or -dependent mechanism depending on the involvement of apoptosis. Molecular insights revealed that hyperactivation of the PIK3C3/VPS34-BECN1 complex increases lysosomal disparity and enhances mitophagy. These changes are followed by reduced mitochondrial biogenesis and by secondary signals that enable superactivated, nonselective or bulk autophagy, leading to ACD. Although the evidence is limited, this review focuses on molecular insights into vorinostat-regulated ACD and describes critical concepts for clinical translation.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Keywords: Autophagy; Cancer; Cell death; Histone deacetylases; Vorinostat

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this pa

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