Rare flavanone-diarylheptanoid hybrids from Typha angustifolia shows anti breast cancer activity via activating TGF-β1/Smad signaling pathway

Four new flavanone-diarylheptanoid hetero dimers, typhatifolins A-D (1-4), were separated from the pollen of a widely distributed medicinal plant Typha angustifolia. Structures of these rare hybrids were elucidated by detailed interpretation of spectroscopic data, and their absolute configurations were determined on the basis of Mosher's method and ECD analyses. All the four compounds showed moderate to significant cytotoxicities against a panel of tumor cell lines with IC₅₀ values ranging from 0.67 to 12.48 μM. Further in vitro antitumor evaluation for typhatifolin B (TTB, 2) on two breast Cancer cells (4T1 and MDA-MB231) revealed that it could remarkably induce cell Apoptosis and G₀/G₁ cycle arrest, as well as block cell migration and invasion. Mechanistically, TTB could exert its antitumor effect via activating the TGF-β1 (transforming growth factor beta 1) signaling pathway as evidenced by RNA-seq analysis and immunoblotting experiments, which was further corroborated by treating Cancer cells with a TGF-β signaling inhibitor. Lastly, the in vivo anti breast Cancer activity was demonstrated by applying the mixture of typhatifolins A-D to a preclinical animal model.

Breast cancer; Diarylheptanoid; Flavanone-diarylheptanoid; TGF-β1/Smad signaling; Typha angustifolia; Typhatifolin.