Candesartan cilexetil as a repurposed therapeutic candidate for nasopharyngeal carcinoma: Integrated in vitro and in silico analyses
DOI:
https://doi.org/10.17179/excli2025-9094Keywords:
nasopharyngeal carcinoma, drug repurposing, candesartan cilexetil, angiotensin II type 1 receptor, MAPK signaling, molecular dynamics simulationAbstract
Nasopharyngeal carcinoma (NPC) is prevalent in East and Southeast Asia and is often diagnosed at advanced stages, where current treatment options are limited and associated with high relapse rates and toxicity. Repurposing clinically approved drugs provides a rapid, cost-effective strategy to identify new therapeutic interventions. Here, we investigated candesartan cilexetil (CC), an angiotensin II type 1 receptor (AT1R) blocker widely used for hypertension (13), for its potential anti-cancer effects in NPC. In vitro assays were performed to assess cell viability, proliferation, clonogenic survival, migration, cell-cycle distribution, and epithelial–mesenchymal transition (EMT) marker expression. Molecular mechanisms were examined via immunoblotting of AT1R and downstream MAPK and PI3K–AKT pathways. In silico molecular dynamics (MD) simulations were conducted to characterize CC–AT1R binding. We found that CC significantly decreased NPC cell viability and proliferation in a concentration-dependent manner, while exhibiting lower cytotoxicity toward immortalized nasopharyngeal epithelial cells. CC inhibited colony formation, induced G0/G1 cell-cycle arrest, and suppressed migration. EMT markers were differentially regulated, with consistent downregulation of vimentin and Slug but paradoxical cadherin changes, indicating context-dependent EMT modulation. Mechanistically, CC downregulated AT1R expression, reduced phosphorylation of p38 MAPK, and enhanced AKT phosphorylation, suggesting compensatory survival signaling. MD simulations confirmed stable CC–AT1R binding, identifying key residues critical for ligand stabilization. Therefore, CC exerts multi-faceted inhibitory effects on NPC cells through AT1R blockade and downstream modulation of oncogenic pathways. The integration of in vitro and in silico analyses highlights CC as a promising repurposed therapeutic candidate for NPC and supports further preclinical evaluation.
Downloads
Published
How to Cite
License
Copyright (c) 2026 Chawalit Ngernsombat, Utid Suriya, Somsiri Udompaisarn, Natta Panomchoeng, Tavan Janvilisri
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish in this journal agree to the following terms:
- The authors keep the copyright and grant the journal the right of first publication under the terms of the Creative Commons Attribution license, CC BY 4.0. This licencse permits unrestricted use, distribution and reproduction in any medium, provided that the original work is properly cited.
- The use of general descriptive names, trade names, trademarks, and so forth in this publication, even if not specifically identified, does not imply that these names are not protected by the relevant laws and regulations.
- Because the advice and information in this journal are believed to be true and accurate at the time of publication, neither the authors, the editors, nor the publisher accept any legal responsibility for any errors or omissions presented in the publication. The publisher makes no guarantee, express or implied, with respect to the material contained herein.
- The authors can enter into additional contracts for the non-exclusive distribution of the journal's published version by citing the initial publication in this journal (e.g. publishing in an institutional repository or in a book).
