Nuplazid suppresses esophageal squamous cell carcinoma growth in vitro and in vivo by targeting PAK4.

Abstract

BACKGROUND:

Due to the high recurrence and low 5-year survival rates of esophageal squamous cell carcinoma (ESCC) after treatment, the discovery of novel drugs for recurrence chemoprevention is of particular importance.

METHODS:

We screened the FDA-approved drug library and found that Nuplazid, an atypical antipsychotic that acts as an effective 5-HT 2 A receptor inverse agonist, could potentially exert anticancer effects in vitro and in vivo on ESCC.

RESULTS:

Pull-down results indicated that Nuplazid binds with p21-activated kinase 4 (PAK4), and a kinase assay showed that Nuplazid strongly suppressed PAK4 kinase activity. Moreover, Nuplazid exhibited inhibitory effects on ESCC in vivo.

CONCLUSIONS:

Our findings indicate that Nuplazid can suppress ESCC progression through targeting PAK4.

• Authors: Yaxing Wei, Wenjie Wu, Yanan Jiang, Hao Zhou, Yin Yu, Lili Zhao, Xiangyu Wu, Xuebo Lu, Qiang Yuan, Zitong Wang, Zigang Dong, Luyun He, Jimin Zhao, Kangdong Liu
• Journal: British journal of cancer (Br J Cancer) Vol. 126 Issue 7 Pg. 1037-1046 (04 2022) ISSN: 1532-1827 [Electronic] England
• PMID: 34912075 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Piperidines
• Urea
• PAK4 protein, human
• p21-Activated Kinases
• pimavanserin

Topics

• Cell Line, Tumor
• Cell Proliferation
• Esophageal Neoplasms (metabolism)
• Esophageal Squamous Cell Carcinoma (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Piperidines
• Urea (analogs & derivatives)
• p21-Activated Kinases (metabolism)