Publication: 3-Hydroxy-β-ionone Suppresses Breast Cancer Progression by Inducing Apoptosis and Blocking EMT Through the TGF-β/Smad Signaling Pathway
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Issued Date
2025-09-01
Resource Type
ISSN
16616596
eISSN
14220067
Scopus ID
2-s2.0-105017128685
Journal Title
International Journal of Molecular Sciences
Volume
26
Issue
18
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Molecular Sciences Vol.26 No.18 (2025)
Suggested Citation
Sutana P., Luetragoon T., Buakaew W., Daotak K., Nilsri N., Thongsri Y., Potup P., Léon C., Usuwanthim K. 3-Hydroxy-β-ionone Suppresses Breast Cancer Progression by Inducing Apoptosis and Blocking EMT Through the TGF-β/Smad Signaling Pathway. International Journal of Molecular Sciences Vol.26 No.18 (2025). doi:10.3390/ijms26188771 Retrieved from: https://hdl.handle.net/20.500.14740/50574
Corresponding Author(s)
Other Contributor(s)
Abstract
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, with limited treatment options and a poor prognosis. Epithelial-to-mesenchymal transition (EMT) plays a critical role in promoting TNBC metastasis. The natural bioactive substance 3-hydroxy-β-ionone (3-HBI), which has been studied in other cancer types, has not yet been examined in TNBC. This study investigates its potential mechanisms in TNBC cells through a combination of computational and experimental approaches, focusing on apoptosis induction and EMT inhibition. Molecular docking and molecular dynamics simulations demonstrated strong and stable binding of 3-HBI to key apoptosis-related proteins (Bcl-2, Bax, caspase-3) and EMT regulators (Smad2, Smad3). In vitro, 3-HBI significantly reduced cell viability in MDA-MB-231, T47D, and MCF7 cells, with IC<inf>50</inf> values of 388.40, 185.50, and 113.40 µg/mL, respectively. Moreover, 3-HBI suppressed clonogenic potential, induced apoptosis, and inhibited both migration and invasion. Molecular analysis showed increased expression of Bax, caspase-3, and E-cadherin, and reduced levels of Bcl-2, Smad2, Smad3, and N-cadherin. These findings provide the first mechanistic evidence that 3-HBI exerts anti-TNBC effects by promoting apoptosis and suppressing EMT, highlighting its potential as a promising therapeutic candidate for TNBC treatment.