Polyphyllin I induces ferritinophagy dependent ferroptosis through EZH2 and promotes anti-tumor immunity - 17/05/25

Doi : 10.1016/j.biopha.2025.118165

Mengfei Xu ^a,^b,^{^{1
co-first authors}} , Xiaoyan Yu ^a,^{^{1
co-first authors}} , Luyu Jia ^a,^{^{1
co-first authors}} , Mingnan Ye ^a , Yueyang Zhao ^c , Rui Wang ^a , Qing Tang ^a , Gangxing Zhu ^a , Jicai Chen ^d , Qichun Zhou ^a,^⁎ , Shigui Deng ^e,^⁎ , Sumei Wang ^a,^⁎
^a Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, Department of Oncology, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Chinese Medicine Guangdong Laboratory, State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangzhou, Guangdong 510120, China
^b Beijing An Zhen Hospital of the Capital University of Medical Sciences, Beijing 100029, China
^c Department of Hematology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, China
^d Department of Thoracic Surgery, Guangdong Province Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, China
^e Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou 510006, China

^⁎Corresponding authors.

Abstract

Background

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.

Results

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.

Conclusion

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.

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Abbreviations : NSCLC, PPI, EZH2, NCOA4, ROS, GPX4, NRF2, FTH1, DAMPs, HMGB-1

Keywords : Polyphyllin I, Non-small cell lung cancer (NSCLC), Ferroptosis, EZH2

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Article 118165- juin 2025 Retour au numéro

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Polyphyllin I induces ferritinophagy dependent ferroptosis through EZH2 and promotes anti-tumor immunity - 17/05/25

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