PMID- 30634582
OWN - NLM
STAT- MEDLINE
DCOM- 20190423
LR  - 20200225
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 20
IP  - 2
DP  - 2019 Jan 10
TI  - Efficacy of Azatyrosine-Phenylbutyric Hydroxamides, a Histone Deacetylase 
      Inhibitor, on Chemotherapy-Induced Gastrointestinal Mucositis.
LID - 10.3390/ijms20020249 [doi]
LID - 249
AB  - 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-alpha (TNF-alpha). 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-alpha, and IL-6 
      production and provide opportunities for the development of new anti-inflammatory 
      drugs targeting mucositis.
FAU - Liao, Po-Lin
AU  - Liao PL
AD  - Institute of Food Safety and Health Risk Assessment, School of Pharmaceutical 
      Sciences, National Yang-Ming University, Taipei 11221, Taiwan. plliao@ym.edu.tw.
AD  - School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, 
      Taiwan. plliao@ym.edu.tw.
FAU - Huang, Shih-Hsuan
AU  - Huang SH
AD  - School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, 
      Taiwan. a001ou@gmail.com.
FAU - Hung, Chien-Hung
AU  - Hung CH
AD  - Department of Pharmacology, School of Medicine, College of Medicine, Taipei 
      Medical University, Taipei 11031, Taiwan. zaq8810@gmail.com.
AD  - Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical 
      University, Taipei 11031, Taiwan. zaq8810@gmail.com.
FAU - Huang, Wei-Kuang
AU  - Huang WK
AD  - School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, 
      Taiwan. garasaba@gmail.com.
FAU - Tsai, Chi-Hao
AU  - Tsai CH
AD  - Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 
      10051, Taiwan. d01447001@ntu.edu.tw.
FAU - Kang, Jaw-Jou
AU  - Kang JJ
AD  - Institute of Food Safety and Health Risk Assessment, School of Pharmaceutical 
      Sciences, National Yang-Ming University, Taipei 11221, Taiwan. jjkang@ntu.edu.tw.
FAU - Wang, Hui-Po
AU  - Wang HP
AD  - School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, 
      Taiwan. hpw@tmu.edu.tw.
FAU - Cheng, Yu-Wen
AU  - Cheng YW
AUID- ORCID: 0000-0003-3714-0464
AD  - School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, 
      Taiwan. ywcheng@tmu.edu.tw.
LA  - eng
GR  - 102-EC-17-A-20-S1-196/Ministry of Economic Affairs of Taiwan/
PT  - Journal Article
DEP - 20190110
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0XTS2H0JH1 (beta-(5-hydroxy-2-pyridyl)alanine)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Alanine/*analogs & derivatives/chemistry
MH  - Animals
MH  - Anti-Inflammatory Agents/chemistry/pharmacology
MH  - Antineoplastic Agents/*adverse effects
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/drug effects
MH  - Histone Deacetylase Inhibitors/chemistry/*pharmacology
MH  - *Hydroxamic Acids/chemistry
MH  - Inhibitory Concentration 50
MH  - Male
MH  - Mice
MH  - Molecular Structure
MH  - Mucositis/drug therapy/*etiology/*pathology
MH  - Rats
PMC - PMC6359543
OTO - NOTNLM
OT  - anti-inflammation
OT  - azatyrosine-phenylbutyric hydroxamides (PBHA)
OT  - histone deacetylase inhibitor (HDACi)
OT  - mucositis
COIS- The authors declare no conflicts of interest.
EDAT- 2019/01/13 06:00
MHDA- 2019/04/24 06:00
PMCR- 2019/01/01
CRDT- 2019/01/13 06:00
PHST- 2018/11/22 00:00 [received]
PHST- 2018/12/27 00:00 [revised]
PHST- 2019/01/06 00:00 [accepted]
PHST- 2019/01/13 06:00 [entrez]
PHST- 2019/01/13 06:00 [pubmed]
PHST- 2019/04/24 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - ijms20020249 [pii]
AID - ijms-20-00249 [pii]
AID - 10.3390/ijms20020249 [doi]
PST - epublish
SO  - Int J Mol Sci. 2019 Jan 10;20(2):249. doi: 10.3390/ijms20020249.