Efficacy of Azatyrosine-Phenylbutyric Hydroxamides, a Histone Deacetylase Inhibitor, on Chemotherapy-Induced Gastrointestinal Mucositis.
Po-Lin LiaoShih-Hsuan HuangChien-Hung HungWei-Kuang HuangChi-Hao TsaiJaw-Jou KangHui-Po WangYu-Wen ChengPublished in: International journal of molecular sciences (2019)
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.
Keyphrases
- chemotherapy induced
- signaling pathway
- histone deacetylase
- pi k akt
- rheumatoid arthritis
- weight loss
- radiation induced
- epithelial mesenchymal transition
- cell proliferation
- induced apoptosis
- anti inflammatory drugs
- primary care
- body mass index
- metabolic syndrome
- adipose tissue
- south africa
- squamous cell carcinoma
- skeletal muscle
- electronic health record
- artificial intelligence
- atomic force microscopy
- locally advanced
- dendritic cells
- cancer therapy
- deep learning