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

IF 6.9 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy Pub Date : 2025-05-12 DOI:10.1016/j.biopha.2025.118165

Mengfei Xu , Xiaoyan Yu , Luyu Jia , Mingnan Ye , Yueyang Zhao , Rui Wang , Qing Tang , Gangxing Zhu , Jicai Chen , Qichun Zhou , Shigui Deng , Sumei Wang

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引用次数: 0

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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聚茶碱I通过EZH2诱导铁蛋白依赖性铁凋亡，促进抗肿瘤免疫

摘要多叶树素I （polyphyllin I， PPI）是临床常用药物多叶树中提取的主要活性成分，具有良好的抗肿瘤活性。因此，本研究的目的是探讨其促进铁下垂和增强抗肿瘤免疫的抗肿瘤特性。结果PPI能有效抑制非小细胞肺癌细胞的增殖，并通过诱导铁下垂引发细胞死亡。此外，通过自噬降解铁在介导ppi诱导的非小细胞肺癌中起关键作用。值得注意的是，EZH2成为PPI的潜在关键靶点，其过表达可显著降低PPI的治疗效果。最后，这些机制的见解和途径在动物模型中得到证实，我们初步揭示了PPI在增强抗肿瘤免疫中的刺激作用。结论ppi通过下调EZH2，促进NCOA4/铁蛋白介导的铁蛋白自噬，并通过促进CD8 +T向肿瘤组织浸润来增强抗肿瘤免疫，从而引发NSCLC铁细胞凋亡。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomedicine & Pharmacotherapy 医学-药学

CiteScore

11.90

自引率

2.70%

发文量

1621

审稿时长

48 days

期刊介绍： Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.