Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma

Yubing Zhou; Xinyu He; Yanan Jiang; Zitong Wang; Yin Yu; Wenjie Wu; Chenyang Zhang; Jincheng Li; Yaping Guo; Xinhuan Chen; Zhicai Liu; Jimin Zhao; Kangdong Liu; Zigang Dong

doi:10.1007/s11684-022-0956-8

Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma

Front Med. 2023 Apr;17(2):290-303. doi: 10.1007/s11684-022-0956-8. Epub 2022 Dec 29.

Authors

Yubing Zhou^#^{1

2}, Xinyu He^#^{1

2}, Yanan Jiang^#^{1

2

3

4}, Zitong Wang¹, Yin Yu^{1

2}, Wenjie Wu^{1

2}, Chenyang Zhang¹, Jincheng Li¹, Yaping Guo^{1

3}, Xinhuan Chen^{1

3}, Zhicai Liu^{4

5}, Jimin Zhao^{1

3

4

6}, Kangdong Liu^{7

8

9

10

11}, Zigang Dong^{12

13

14

15}

Affiliations

¹ The Pathophysiology Department, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China.
² The China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450000, China.
³ State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, 450000, China.
⁴ Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, 450000, China.
⁵ Oncology Department, The Tumor Hospital of Linzhou City, Linzhou, 456500, China.
⁶ Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, 450000, China.
⁷ The Pathophysiology Department, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China. kdliu@zzu.edu.cn.
⁸ The China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450000, China. kdliu@zzu.edu.cn.
⁹ State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, 450000, China. kdliu@zzu.edu.cn.
¹⁰ Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, 450000, China. kdliu@zzu.edu.cn.
¹¹ Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, 450000, China. kdliu@zzu.edu.cn.
¹² The Pathophysiology Department, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China. dongzg@zzu.edu.cn.
¹³ The China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450000, China. dongzg@zzu.edu.cn.
¹⁴ State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, 450000, China. dongzg@zzu.edu.cn.
¹⁵ Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, 450000, China. dongzg@zzu.edu.cn.

^# Contributed equally.

PMID: 36580233
DOI: 10.1007/s11684-022-0956-8

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

Keywords: benzydamine; cyclin-dependent kinase 2; esophageal squamous cell carcinoma; patient-derived xenograft.

MeSH terms

Apoptosis
Benzydamine*
Cell Line, Tumor
Cell Proliferation
Cyclin-Dependent Kinase 2
Esophageal Neoplasms* / drug therapy
Esophageal Squamous Cell Carcinoma* / drug therapy
Humans
Molecular Docking Simulation
Phosphorylation

Substances

Benzydamine
CDK2 protein, human
Cyclin-Dependent Kinase 2