Polygonum multiflorum Stilbene Glycoside Oligomers induce the ferroptosis of triple negative breast cancer cells

The quality control testing component and main active ingredient of Polygonum multiflorum Thunb. (P. multiflorum), known as trans-2,3,5,4'-tetrahydroxystilbene 2-O-β-D-glucopyranoside (TSG), exhibits diverse biological activities. In this study, we report, for the first time, the potent ability of TSG to induce ferroptosis in triple negative breast cancer (TNBC) cell lines and to inhibit the proliferation of TNBC cells. Treatment with TSG triggers the production of lipid peroxides, 4-hydroxynonenal (4-HNE), and reactive oxygen species (ROS) in TNBC cells, indicating the induction of ferroptosis. Both in vivo and in vitro experiments confirmed the inhibitory effects of TSG on TNBC cell proliferation and metastasis. Furthermore, we investigated the effects of other stilbene glycoside oligomers, alongside TSG, on TNBC cell lines. These compounds also demonstrated the ability to induce ferroptosis and suppress TNBC cells' proliferation and metastasis. These findings suggest that the induction of ferroptosis by TSG and related compounds could potentially serve as a promising therapeutic strategy for TNBC treatment.