三七中的一种天然原三七酚通过上调 ASCL4 增强骨肉瘤对铁中毒的敏感性

IF 3.8 2区农林科学 Q2 FOOD SCIENCE & TECHNOLOGY

Journal of Functional Foods Pub Date : 2024-09-30 DOI:10.1016/j.jff.2024.106488

Zhuo Chen, Renhua Ni, Yuanyu Hu, Yiyuan Yang, Yun Tian

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引用次数: 0

摘要

骨肉瘤是最常见的原发性骨癌，目前的治疗方法包括手术、放疗和化疗，但对转移性和化疗耐药病例基本无效，因此需要新型疗法。在这项研究中，我们研究了(20S)-Protopanaxatriol [(20S)-PPT]--一种来自三七的天然产物，三七是一种既可食用又可药用的草药--是否能增强骨肉瘤对由RSL3、ML210和IKE等诱导剂诱导的铁变态反应的敏感性。具体来说，(20S)-PPT 增加了暴露于 RSL3 的骨肉瘤细胞的脂质过氧化反应。这种效应是由ACSL4上调介导的，因为ACSL4敲除可逆转（20S）-PPT敏化的铁变态反应。重要的是，(20S)-PPT 与 IKE 联用可显著降低异种移植模型中的肿瘤生长。总之，我们的研究证实，将（20S）-PPT 与铁突变诱导剂结合使用，为治疗骨肉瘤提供了一种前景广阔的新策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

A natural protopanaxatriol from Panax notoginseng enhances osteosarcoma sensitivity to ferroptosis via ASCL4 upregulation

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A natural protopanaxatriol from Panax notoginseng enhances osteosarcoma sensitivity to ferroptosis via ASCL4 upregulation

Current treatments for osteosarcoma, the most common primary bone cancer, including surgery, radiotherapy, and chemotherapy, are largely ineffective against metastatic and chemo-resistant cases, emphasizing the need for novel therapies. In this study, we investigated (20S)-Protopanaxatriol [(20S)-PPT], a natural product from Panax notoginseng, an herb used both as food and medicine, for its ability to enhance osteosarcoma sensitivity to ferroptosis induced by inducers such as RSL3, ML210, and IKE. Specifically, (20S)-PPT increased lipid peroxidation in osteosarcoma cells exposed to RSL3. This effect was mediated by ACSL4 upregulation, as ACSL4 knockdown reversed (20S)-PPT-sensitized ferroptosis. Importantly, (20S)-PPT significantly reduced tumor growth in xenograft models when combined with IKE. Collectively, our study confirms that combining (20S)-PPT with ferroptosis inducers offers a promising novel strategy for treating osteosarcoma.

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来源期刊

Journal of Functional Foods FOOD SCIENCE & TECHNOLOGY-

CiteScore

9.60

自引率

1.80%

发文量

428

审稿时长

76 days

期刊介绍： Journal of Functional Foods continues with the same aims and scope, editorial team, submission system and rigorous peer review. We give authors the possibility to publish their top-quality papers in a well-established leading journal in the food and nutrition fields. The Journal will keep its rigorous criteria to screen high impact research addressing relevant scientific topics and performed by sound methodologies. The Journal of Functional Foods aims to bring together the results of fundamental and applied research into healthy foods and biologically active food ingredients. The Journal is centered in the specific area at the boundaries among food technology, nutrition and health welcoming papers having a good interdisciplinary approach. The Journal will cover the fields of plant bioactives; dietary fibre, probiotics; functional lipids; bioactive peptides; vitamins, minerals and botanicals and other dietary supplements. Nutritional and technological aspects related to the development of functional foods and beverages are of core interest to the journal. Experimental works dealing with food digestion, bioavailability of food bioactives and on the mechanisms by which foods and their components are able to modulate physiological parameters connected with disease prevention are of particular interest as well as those dealing with personalized nutrition and nutritional needs in pathological subjects.