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.
authors.affiliation: Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX 77030, USA. yyang@tmhs.org
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Joy
authors.initials: J
authors.lastname: Wolfram
authors.forename: Haifa
authors.initials: H
authors.lastname: Shen
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Fang
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006569:Hesperidin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D016212:Transforming Growth Factor beta; D006569:Hesperidin; C013015:hesperetin