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Polyphyllin I is a **steroidal saponin** isolated from the rhizome of *Paris polyphylla* (Chong Lou) and other related species[8][2][1]. It exhibits potent **anticancer** activity by inducing cell death, inhibiting proliferation, and limiting invasion in diverse tumor cell lines including liver, breast, lung, gastric, colon, and osteosarcoma cells[3][4][6][8][9]. Mechanistically, polyphyllin I triggers multiple types of regulated cell death:\n- **Apoptosis:** Promotes programmed cell death in various tumor models[1][4].\n- **Autophagic cell death:** Induces autophagy via increased reactive oxygen species (ROS) and suppression of AKT/mTOR signaling[9].\n- **Ferroptosis:** Promotes iron-dependent oxidative cell death by modulating NRF2/FTH1 pathway and increasing lipid peroxidation[7]. Additional effects include impairment of tumor vasculature by inhibiting vasculogenic mimicry (the PI3K-Akt-Twist1-VE-cadherin pathway)[3], and suppression of STAT3 phosphorylation in gastric cancer cells[4]. Polyphyllin I is primarily used experimentally and in traditional Chinese medicine; clinical development is ongoing, focusing predominantly on oncology indications[3][4][7][8][9].
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