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

Br J Cancer. 2022 Apr;126(7):1037-1046. doi: 10.1038/s41416-021-01651-z. Epub 2021 Dec 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

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