Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 58, Issue -, Pages 390-395Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2012.10.028
Keywords
Hesperetin; TGF-beta inhibition; Atomic force microscopy; Single-molecule fluorescence imaging
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Funding
- Ernest Cockrell Jr. Distinguished Endowed Chair
- US Department of Defense [W81XWH-09-1-0212]
- National Institute of Health [U54CA143837, U54CA151668]
- National Basic Research Program of China [2007CB935601]
- National Natural Science Foundation of China [90713024, 20821003]
- Chinese Academy of Sciences
- Nylands Nation Finland
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We have identified a previously unknown function of the natural compound, hesperetin. Here, we demonstrate that this small molecular agent is able to inhibit the transforming growth factor-beta (TGF-beta) signaling pathway. Single-molecule force measurements and single-molecule fluorescence imaging show that hesperetin interferes with ligand receptor interactions. Furthermore, by Western blot analysis, it was confirmed that hesperetin also inhibits the phosphorylation of Smad3, a down-stream target of the TGF-beta pathway. In addition we demonstrated that this compound hinders TGF-beta 1-induced cancer cell migration and invasion. These results suggest a potential future application for hesperetin as a TGF-beta inhibitor in cancer therapy. (C) 2012 Elsevier Masson SAS. All rights reserved.
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