The histone deacetylase inhibitor panobinostat exerts anticancer effects on esophageal squamous cell carcinoma cells by inducing cell cycle arrest

In this study, HDACIs were initially considered to have anticancer activity for ESCC, due to the high expression of HDAC genes in ESCC cell lines by analysing expression data of 27 ESCC cell lines from the Broad ‐Novartis Cancer Cell Line Encyclopedia. Next, we used five ESCC cell lines and one normal immortalized esophageal epithelial cell line to screen three HDACIs, panobinostat (LBH589), vorinostat (SAHA), and trichostatin A (TSA), for the ability to inhibit growth. Here, we report that LBH589 more ef fectively suppressed cell proliferation of ESCC cell lines, in a dose‐dependent manner, than TSA and SAHA, as well as had lower toxicity against the SHEE normal immortalized esophageal epithelial cell line. Further experiments indicated that LBH589 treatment significantly inhibited TP53 (mutated T P53) expression, both at the mRNA and protein level, and simultaneously increased p21 and decreased cyclin D1 expression. Taken together, we propose that LBH589 inhibits ESCC cell proliferation mainly through inducing cell cycle arrest by increasing p21 and decreasing cyclin D1 in a p53‐independen t manner.Significance of the studyIn this study, the antitumor activity of HDACIs LBH589, SAHA, and TSA on ESCC was characterized, with LBH589 displaying the most potent anti ‐proliferative activity while not harming normal immortalized esophageal epithelial cells. Furthermore, we propose that LBH589 exerts its anti‐proliferative effect by inducing cell cycle arrest. The ability...

Source: Cell Biochemistry and Function - November 28, 2018 Category: Biochemistry Authors: Yin ‐Wei Cheng, Lian‐Di Liao, Qian Yang, Yang Chen, Ping‐Juan Nie, Xiao‐Jun Zhang, Jian‐Jun Xie, Bao‐En Shan, Lian‐Mei Zhao, Li‐Yan Xu, En‐Min Li Tags: RESEARCH ARTICLE Source Type: research