RESEARCH ARTICLE The histone deacetylase inhibitor panobinostat exerts anticancer effects on esophageal squamous cell carcinoma cells by inducing cell cycle arrest Yin‐Wei Cheng 1,2 | Lian‐Di Liao 1,3 | Qian Yang 1,2 | Yang Chen 1,2 | Ping‐Juan Nie 1,2 | Xiao‐Jun Zhang 1,2 | Jian‐Jun Xie 1,2 | Bao‐En Shan 4 | Lian‐Mei Zhao 4 | Li‐Yan Xu 1,3 | En‐Min Li 1,2 1 The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, China 2 Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, China 3 Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, China 4 Research Centre, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China Correspondence En‐Min Li and Li‐Yan Xu, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China. Email: nmli@stu.edu.cn; lyxu@stu.edu.cn Funding information National Cohort of Esophageal Cancer of China, Grant/Award Number: 2016YFC09014000; National Natural Science Foundation of China, Grant/Award Number: No. 81472613 No. 81602630 No. 81772532; Natural Science Foundation of China‐Guangdong Joint Fund, Grant/Award Number: U1601229 Esophageal squamous cell carcinoma (ESCC) is a common malignancy without effec- tive therapy. Histone deacetylase inhibitors (HDACIs) have been demonstrated as an emerging class of anticancer drugs for a range of haematological and solid tumours. However, the effect of HDACIs has not yet been investigated on ESCC cells. 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 effectively 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 TP53) 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 prolifer- ation mainly through inducing cell cycle arrest by increasing p21 and decreasing cyclin D1 in a p53‐independent manner. Significance of the study: In 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 to specifically target cancer cells indicates therapeutic potential for use of LBH589 in the treatment of ESCC. KEYWORDS cell cycle, esophageal squamous cell carcinoma (ESCC), HDAC inhibitors (HDACIs), panobinostat (LBH589), TP53 Received: 30 July 2018 Accepted: 18 September 2018 DOI: 10.1002/cbf.3359 Cell Biochem Funct. 2018;1–10. © 2018 John Wiley & Sons, Ltd. wileyonlinelibrary.com/journal/cbf 1