Polyphyllin I induces ferritinophagy dependent ferroptosis through EZH2 and promotes anti-tumor immunity

Polyphyllin I (PPI), the primary active component extracted from the commonly utilized drug Paris polyphylla, in clinical applications, exhibits exceptional anti-tumor activity. Therefore, the objective of this study is to delve into its antitumor properties by promoting ferroptosis and enhancing anti-tumor immunity.

Our result demonstrate that PPI effectively suppresses the proliferation of NSCLC cells and triggers their demise through the induction of ferroptosis. Furthermore, the degradation of iron via autophagy is pivotal in mediating PPI-induced ferroptosis in NSCLC. Notably, EZH2 emerges as a potential key target of PPI, and its overexpression can significantly attenuate the therapeutic efficacy of PPI. Lastly, these mechanistic insights and pathways were corroborated in animal model, and we preliminarily revealing a stimulatory role of PPI in bolstering anti-tumor immunity.

PPI triggers ferroptosis in NSCLC by downregulating EZH2, promoting NCOA4/Ferritin mediated ferritinophagy, and enhances anti-tumor immunity by promoting CD8 +T infiltration into tumor tissue.