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Int. J. Mol. Sci. 2017, 18(9), 1883;

Histone Deacetylase Inhibitor-Induced Autophagy in Tumor Cells: Implications for p53

Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Waldeyerstrasse 15, 48149 Münster, Germany
Department of Cranio-Maxillofacial Surgery, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany
Author to whom correspondence should be addressed.
Received: 28 July 2017 / Revised: 20 August 2017 / Accepted: 28 August 2017 / Published: 31 August 2017
(This article belongs to the Special Issue Autophagy at the Intersection of the Immune System and Cancer)
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Autophagy is an essential process of the eukaryotic cell allowing degradation and recycling of dysfunctional cellular components in response to either physiological or pathological changes. Inhibition of autophagy in combination with chemotherapeutic treatment has emerged as a novel approach in cancer treatment leading to cell cycle arrest, differentiation, and apoptosis. Suberoyl hydroxamic acid (SAHA) is a broad-spectrum histone deacetylase inhibitor (HDACi) suppressing family members in multiple HDAC classes. Increasing evidence indicates that SAHA and other HDACi can, in addition to mitochondria-mediated apoptosis, also promote caspase-independent autophagy. SAHA-induced mTOR inactivation as a major regulator of autophagy activating the remaining autophagic core machinery is by far the most reported pathway in several tumor models. However, the question of which upstream mechanisms regulate SAHA-induced mTOR inactivation that consequently initiate autophagy has been mainly left unexplored. To elucidate this issue, we recently initiated a study clarifying different modes of SAHA-induced cell death in two human uterine sarcoma cell lines which led to the conclusion that the tumor suppressor protein p53 could act as a molecular switch between SAHA-triggered autophagic or apoptotic cell death. In this review, we present current research evidence about HDACi-mediated apoptotic and autophagic pathways, in particular with regard to p53 and its therapeutic implications. View Full-Text
Keywords: HDAC; HDACi; SAHA; Autophagy; p53; Apoptosis; Tumor HDAC; HDACi; SAHA; Autophagy; p53; Apoptosis; Tumor

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Mrakovcic, M.; Kleinheinz, J.; Fröhlich, L.F. Histone Deacetylase Inhibitor-Induced Autophagy in Tumor Cells: Implications for p53. Int. J. Mol. Sci. 2017, 18, 1883.

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