Hesperetin: An inhibitor of the transforming growth factor-β (TGF-β) signaling pathway

Yong Yang; Joy Wolfram; Haifa Shen; Xiaohong Fang; Mauro Ferrari

doi:10.1016/j.ejmech.2012.10.028

Hesperetin: An inhibitor of the transforming growth factor-β (TGF-β) signaling pathway

Yong Yang, Joy Wolfram, Haifa Shen, Xiaohong Fang, Mauro Ferrari

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

Abstract

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-β (TGF-β) 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-β pathway. In addition we demonstrated that this compound hinders TGF-β1-induced cancer cell migration and invasion. These results suggest a potential future application for hesperetin as a TGF-β inhibitor in cancer therapy.

Original language	English (US)
Pages (from-to)	390-395
Number of pages	6
Journal	European Journal of Medicinal Chemistry
Volume	58
DOIs	https://doi.org/10.1016/j.ejmech.2012.10.028
State	Published - Dec 2012

Keywords

Atomic force microscopy
Hesperetin
Single-molecule fluorescence imaging
TGF-β inhibition

ASJC Scopus subject areas

Drug Discovery
Organic Chemistry
Pharmacology

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10.1016/j.ejmech.2012.10.028

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title = "Hesperetin: An inhibitor of the transforming growth factor-β (TGF-β) signaling pathway",

abstract = "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-β (TGF-β) 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-β pathway. In addition we demonstrated that this compound hinders TGF-β1-induced cancer cell migration and invasion. These results suggest a potential future application for hesperetin as a TGF-β inhibitor in cancer therapy.",

keywords = "Atomic force microscopy, Hesperetin, Single-molecule fluorescence imaging, TGF-β inhibition",

author = "Yong Yang and Joy Wolfram and Haifa Shen and Xiaohong Fang and Mauro Ferrari",

note = "Funding Information: The authors acknowledge supports from the following funding sources: Ernest Cockrell Jr. Distinguished Endowed Chair (M.F.), US Department of Defense ( W81XWH-09-1-0212 ) (M.F.), National Institute of Health ( U54CA143837 , U54CA151668 ) (M.F.), National Basic Research Program of China ( 2007CB935601 ) (X.F.), National Natural Science Foundation of China (Nos 90713024 , 20821003 ) (X.F.), Chinese Academy of Sciences (X.F.) and Nylands Nation Finland (J.W.). ",

year = "2012",

month = dec,

doi = "10.1016/j.ejmech.2012.10.028",

language = "English (US)",

volume = "58",

pages = "390--395",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

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TY - JOUR

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T2 - An inhibitor of the transforming growth factor-β (TGF-β) signaling pathway

AU - Yang, Yong

AU - Wolfram, Joy

AU - Shen, Haifa

AU - Fang, Xiaohong

AU - Ferrari, Mauro

N1 - Funding Information: The authors acknowledge supports from the following funding sources: Ernest Cockrell Jr. Distinguished Endowed Chair (M.F.), US Department of Defense ( W81XWH-09-1-0212 ) (M.F.), National Institute of Health ( U54CA143837 , U54CA151668 ) (M.F.), National Basic Research Program of China ( 2007CB935601 ) (X.F.), National Natural Science Foundation of China (Nos 90713024 , 20821003 ) (X.F.), Chinese Academy of Sciences (X.F.) and Nylands Nation Finland (J.W.).

PY - 2012/12

Y1 - 2012/12

N2 - 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-β (TGF-β) 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-β pathway. In addition we demonstrated that this compound hinders TGF-β1-induced cancer cell migration and invasion. These results suggest a potential future application for hesperetin as a TGF-β inhibitor in cancer therapy.

AB - 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-β (TGF-β) 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-β pathway. In addition we demonstrated that this compound hinders TGF-β1-induced cancer cell migration and invasion. These results suggest a potential future application for hesperetin as a TGF-β inhibitor in cancer therapy.

KW - Atomic force microscopy

KW - Hesperetin

KW - Single-molecule fluorescence imaging

KW - TGF-β inhibition

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ER -

Hesperetin: An inhibitor of the transforming growth factor-β (TGF-β) signaling pathway

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Keywords

ASJC Scopus subject areas

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