Polyphyllin VI is an orally active natural saponin that exerts anticancer effects primarily by inducing cell-cycle arrest, apoptosis, and pyroptosis[1][2]. Polyphyllin VI is commonly used in cancer-mechanism studies, especially those focused on cell-death pathways and their associated signaling cascades[3].
In vitro, treatment of glioma cells with Polyphyllin VI (0-8μM; 12-48h) dose-dependently inhibits cell proliferation, blocks cycle at G2/M, suppresses migration, and induces apoptosis and autophagy[4]. Polyphyllin VI (0-30μM; 48h) inhibits U2OS osteosarcoma proliferation, triggers G2/M arrest, collapses mitochondrial membrane potential, and simultaneously evokes caspase-mediated apoptosis[5].
In vivo, Polyphyllin VI (5mg/kg/day; i.p.; 14 days) reversed bleomycin-induced pulmonary fibrosis in C57BL/6J mice, reduced collagen deposition, suppressed α-SMA and vimentin expression, and restored E-cadherin levels[6]. Polyphyllin VI (10mg/kg/day; i.p.; 10 days) increased NLRP3 inflammasome activation and caspase-1-mediated pyroptosis in A549 tumor xenografts of athymic nude mice[7].
References:
[1] Lin Z, Liu Y, Li F, et al. Anti-lung Cancer Effects of Polyphyllin VI and VII Potentially Correlate with Apoptosis In Vitro and In Vivo. Phytother Res. 2015;29(10):1568-1576.
[2] Liu Y, Dong X, Wang W, et al. Molecular Mechanisms of Apoptosis in HepaRG Cell Line Induced by Polyphyllin VI via the Fas Death Pathway and Mitochondrial-Dependent Pathway. Toxins (Basel). 2018;10(5):201.
[3] Wang Y, Huang X, Xian B, et al. Machine learning and bioinformatics-based insights into the potential targets of saponins in Paris polyphylla smith against non-small cell lung cancer. Front Genet. 2022;13:1005896.
[4] Liu W, Chai Y, Hu L, et al. Polyphyllin VI Induces Apoptosis and Autophagy via Reactive Oxygen Species Mediated JNK and P38 Activation in Glioma. Onco Targets Ther. 2020;13:2275-2288.
[5] Yuan YL, Jiang N, Li ZY, et al. Polyphyllin VI induces apoptosis and autophagy in human osteosarcoma cells by modulation of ROS/JNK activation. Drug Des Devel Ther. 2019;13:3091-3103.
[6] Xie Y, Gan C, Liu H, et al. Polyphyllin VI Ameliorates Pulmonary Fibrosis by Suppressing the MAPK/ERK and PI3K/AKT Signaling Pathways via Upregulating DUSP6. Phytother Res. 2024;38(12):5930-5948.
[7] Teng JF, Mei QB, Zhou XG, et al. Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer. Cancers (Basel). 2020;12(1):193.
















