Next Article in Journal
Dysregulation of Dopaminergic Regulatory Factors TH, Nurr1, and Pitx3 in the Ventral Tegmental Area Associated with Neuronal Injury Induced by Chronic Morphine Dependence
Previous Article in Journal
New Structures and Gating of Voltage-Dependent Potassium (Kv) Channels and Their Relatives: A Multi-Domain and Dynamic Question
Previous Article in Special Issue
Pharmacological Inhibition of Class IIA HDACs by LMK-235 in Pancreatic Neuroendocrine Tumor Cells
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2019, 20(2), 249; https://doi.org/10.3390/ijms20020249

Efficacy of Azatyrosine-Phenylbutyric Hydroxamides, a Histone Deacetylase Inhibitor, on Chemotherapy-Induced Gastrointestinal Mucositis

1
Institute of Food Safety and Health Risk Assessment, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei 11221, Taiwan
2
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
3
Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
4
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
5
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 22 November 2018 / Revised: 27 December 2018 / Accepted: 6 January 2019 / Published: 10 January 2019
(This article belongs to the Special Issue Roles of HDACs and HDAC Inhibitors in Human Cancers)
Full-Text   |   PDF [3046 KB, uploaded 10 January 2019]   |  

Abstract

Gastrointestinal mucositis is a serious side effect of chemotherapy. Currently, no effective treatment exists for chemotherapy-induced mucositis, prompting the need to develop an anti-mucositis agent for use in clinics. The present study investigated whether azatyrosine-PBHA (AzP), a histone deacetylase inhibitor, has a therapeutic effect on intestinal mucosa. The results indicated that AzP did not affect the proliferation and viability of cancer cells, outcomes that are achieved by suberoylanilide hydroxamic acid (SAHA). However, AzP could decrease production of the inflammatory mediators interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor-necrosis factor-α (TNF-α). In vivo histopathological assessment showed that AzP reduced cisplatin-induced injury to the jejunum villi and triggered weight loss in the C57BL/6 mice. Immunohistochemistry (IHC) results demonstrated that mice treated with AzP also recovered from cisplatin-induced injury to the intestinal mucosa. Mechanistic in vitro study using DAVID/KEGG enrichment analysis of microarray data and confirmation by a Western blot indicated the influence of AzP on the MEK/ERK and AKT-dependent pathway. In conclusion, the study demonstrated that AzP might regulate the MEK/ERK MAPK signaling pathway to attenuate MCP-1, TNF-α, and IL-6 production and provide opportunities for the development of new anti-inflammatory drugs targeting mucositis. View Full-Text
Keywords: anti-inflammation; azatyrosine-phenylbutyric hydroxamides (PBHA); histone deacetylase inhibitor (HDACi); mucositis anti-inflammation; azatyrosine-phenylbutyric hydroxamides (PBHA); histone deacetylase inhibitor (HDACi); mucositis
Figures

Figure 1

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).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Liao, P.-L.; Huang, S.-H.; Hung, C.-H.; Huang, W.-K.; Tsai, C.-H.; Kang, J.-J.; Wang, H.-P.; Cheng, Y.-W. Efficacy of Azatyrosine-Phenylbutyric Hydroxamides, a Histone Deacetylase Inhibitor, on Chemotherapy-Induced Gastrointestinal Mucositis. Int. J. Mol. Sci. 2019, 20, 249.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top