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The hidden potential of solasonine: Targeting non-small cell lung cancer (NSCLC) metastasis through GATM and Smad2 pathways.

Authors :
Hu C
Zhang JQ
Zhuang XY
Zhao ZD
Qian XJ
Chen Y
Source :
Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2025 Feb 02; Vol. 139, pp. 156455. Date of Electronic Publication: 2025 Feb 02.
Publication Year :
2025
Publisher :
Ahead of Print

Abstract

Purpose: To study the pharmacological effects of solasonine (Sol) in inhibiting non-small cell lung cancer (NSCLC) metastasis.<br />Methods: The pharmacological effects of solasonine were examined in vitro by continuous induction of NSCLC cells by no treatment, or TGF-β, or creatine. Cell migration and invasion were assessed via wound healing and transwell assays, and the levels of epithelial-mesenchymal transition (EMT) markers were determined using immunofluorescence and Western Blot. Solasonine's ability to bind to TGF-β and creatine transferases and isoenzymes was assessed by TCGA, KMPLOT database, cellular thermal shift assay (CETSA), and molecular docking assay. In vivo, two types of NSCLC cells were injected into mice using the tail vein. Solasonine's effect on tumor metastasis was determined using in vivo fluorescent probes, hematoxylin-eosin staining assay, and immunofluorescence.<br />Results: Unlike traditional therapies targeting TGF-β receptors, Sol was shown to inhibit NSCLC metastasis through a novel mechanism independent of TGF-β signaling. Creatine was found to promote NSCLC metastasis in vitro by enhancing cell migration, invasion, and EMT-related protein expression, and in vivo by increasing metastasis to the liver. These effects were mediated by the activation of Smad2 phosphorylation and EMT independently of TGF-β. Sol effectively counteracted these effects by targeting guanidinoacetate methyltransferase (GATM) with high binding affinity, thereby suppressing the TTK-mediated Smad2 pathway and significantly reducing metastasis to the lungs and liver, as confirmed by HE staining and fluorescence imaging.<br />Conclusions: This study identifies solasonine as a novel inhibitor of NSCLC metastasis, acting through the GATM and Smad2 pathways to counter creatine-induced metastasis. These findings underscore the potential of Sol as a therapeutic candidate for metastatic NSCLC.<br />Competing Interests: Declaration of competing interest The authors declared that they had no competing interests.<br /> (Copyright © 2025 Elsevier GmbH. All rights reserved.)

Details

Language :
English
ISSN :
1618-095X
Volume :
139
Database :
MEDLINE
Journal :
Phytomedicine : international journal of phytotherapy and phytopharmacology
Publication Type :
Academic Journal
Accession number :
39922150
Full Text :
https://doi.org/10.1016/j.phymed.2025.156455