2. Academic Validation
  3. Death by histone deacetylase inhibitor quisinostat in tongue squamous cell carcinoma via apoptosis, pyroptosis, and ferroptosis

Death by histone deacetylase inhibitor quisinostat in tongue squamous cell carcinoma via apoptosis, pyroptosis, and ferroptosis

  • Toxicol Appl Pharmacol. 2021 Jan 1;410:115363. doi: 10.1016/j.taap.2020.115363.
Xinhuan Wang 1,  Ke Liu 1,  Huimin Gong 2,  Dezhi Li 1,  Wenfeng Chu 3,  Dan Zhao 4,  Xiaofeng Wang 5,  Dongyang Xu 6
Affiliations

Affiliations

  • 1 Department of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, PR China.
  • 2 Department of Oral, Dalian Stomatological Hospital, Dalian, Liaoning 116021, PR China.
  • 3 Department of Pharmacology (The State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, PR China.
  • 4 Department of Clinical Pharmacy (Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment), the 2nd Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, PR China.
  • 5 Department of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, PR China. Electronic address: [email protected].
  • 6 Department of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, PR China. Electronic address: [email protected].
PMID: 33290780 DOI: 10.1016/j.taap.2020.115363
Abstract

Tongue Cancer is one of the most common oral malignancies. Quisinostat is a histone deacetylase inhibitor with antitumor activity. The aim of this study was to evaluate the effects of quisinostat on the viability of tongue squamous cell carcinoma (TSCC) cells (CAL-27, TCA-8113) in vitro and in vivo. Cell viability, cell morphological observation, scratch wound-healing assay, transwell migration assay, transmission electron microscope, flow cytometry and cellular Reactive Oxygen Species were assessed in vitro. The results showed that quisinostat can significantly inhibit the viability, growth and migration of TSCC cells. And quisinostat could significantly induce TSCC cells Apoptosis, Pyroptosis, and Ferroptosis. Quisinostat significantly inhibited tumor tissue growth in animal experiments. Up-regulation of the expression of Bax, cleaved-caspase3, Caspase-1, p53, phospho-p53 and down-regulated of the expression of Caspase-3, Bcl-2, GPX4 in cell lines and tumor tissues of nude mice were observed by Western blotting analysis. Up-regulation of the expression of Caspase-1, Bax, cleaved-caspase3, p53 and down-regulated of the expression of ki67, Caspase-3, Bcl-2, GPX4 in tumor tissues of nude mice were observed by immunohistochemistry. TUNEL analysis showed that quisinostat could increase the Apoptosis rate in the tumor tissues of nude mice. Up-regulation of the expression of p53 and down-regulated expression of GPX4 in cell lines were observed by immunofluorescent staining, and the expression locations of p53 and GPX4 proteins in TSCC cells were observed. Based on these findings, quisinostat may be a potential drug for the treatment of tongue squamous cell carcinoma.

Keywords

Apoptosis; Ferroptosis; HDACi; Pyroptosis; Quisinostat; p53.

Figures
Products