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

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.

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► Hesperetin blocks TGFβ ligand–receptor interactions.
► Hesperetin inhibits downstream TGFβ-signaling.
► Hesperetin decreases TGFβ-induced cancer cell migration and invasion.