Pacidusin B isolated from Phyllanthus acidus triggers ferroptotic cell death in HT1080 cells

IF 4.8 3区化学 Q1 CHEMISTRY, MEDICINAL

Natural Products and Bioprospecting Pub Date : 2024-05-23 DOI:10.1007/s13659-024-00454-y

Guangyu Zhu, Dian Luo, Yueqin Zhao, Zhengrui Xiang, Chao Chen, Na Li, Xiaojiang Hao, Xiao Ding, Yingjun Zhang, Yuhan Zhao

{"title":"Pacidusin B isolated from Phyllanthus acidus triggers ferroptotic cell death in HT1080 cells","authors":"Guangyu Zhu, Dian Luo, Yueqin Zhao, Zhengrui Xiang, Chao Chen, Na Li, Xiaojiang Hao, Xiao Ding, Yingjun Zhang, Yuhan Zhao","doi":"10.1007/s13659-024-00454-y","DOIUrl":null,"url":null,"abstract":"<div><p>Cancer cells generally exhibit ‘iron addiction’ phenotypes, which contribute to their vulnerability to ferroptosis inducers. Ferroptosis is a newly discovered form of programmed cell death caused by iron-dependent lipid peroxidation. In the present study, pacidusin B, a dichapetalin-type triterpenoid from <i>Phyllanthus acidus</i> (L.) Skeels (Euphorbiaceae), induces ferroptosis in the HT1080 human fibrosarcoma cell line. Cells treated with pacidusin B exhibited the morphological characteristic ‘ballooning’ phenotype of ferroptosis. The biochemical hallmarks of ferroptosis were also observed in pacidusin B-treated cells. Both oxidative stress and ER stress play significant roles in pacidusin B-induced ferroptosis. The activation of the PERK-Nrf2-HO-1 signaling pathway led to iron overload, while inhibition of GPX4 further sensitized cancer cells to ferroptosis. Furthermore, the molecular docking study showed that pacidusin B docked in the same pocket in xCT as the ferroptosis inducer erastin. These results revealed that pacidusin B exerts anticancer effects via inducing ER-mediated ferroptotic cell death.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"14 1","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11116305/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Natural Products and Bioprospecting","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s13659-024-00454-y","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Cancer cells generally exhibit ‘iron addiction’ phenotypes, which contribute to their vulnerability to ferroptosis inducers. Ferroptosis is a newly discovered form of programmed cell death caused by iron-dependent lipid peroxidation. In the present study, pacidusin B, a dichapetalin-type triterpenoid from Phyllanthus acidus (L.) Skeels (Euphorbiaceae), induces ferroptosis in the HT1080 human fibrosarcoma cell line. Cells treated with pacidusin B exhibited the morphological characteristic ‘ballooning’ phenotype of ferroptosis. The biochemical hallmarks of ferroptosis were also observed in pacidusin B-treated cells. Both oxidative stress and ER stress play significant roles in pacidusin B-induced ferroptosis. The activation of the PERK-Nrf2-HO-1 signaling pathway led to iron overload, while inhibition of GPX4 further sensitized cancer cells to ferroptosis. Furthermore, the molecular docking study showed that pacidusin B docked in the same pocket in xCT as the ferroptosis inducer erastin. These results revealed that pacidusin B exerts anticancer effects via inducing ER-mediated ferroptotic cell death.

Graphical Abstract

Abstract Image

查看原文本刊更多论文

从Phyllanthus acidus中分离出的Pacidusin B能引发HT1080细胞的铁性细胞死亡。

癌细胞通常表现出 "铁成瘾 "表型，这导致它们容易受到铁变态反应诱导剂的影响。铁中毒是一种新发现的细胞程序性死亡形式，由铁依赖性脂质过氧化引起。在本研究中，pacidusin B（一种来自 Phyllanthus acidus (L.) Skeels（大戟科）的二矢车菊苷型三萜类化合物）可诱导 HT1080 人纤维肉瘤细胞系发生铁氧化。用 pacidusin B 处理的细胞表现出铁细胞凋亡的形态特征 "气球 "表型。在经 pacidusin B 处理的细胞中也观察到了铁突变的生化特征。氧化应激和ER应激在pacidusin B诱导的铁突变中都起着重要作用。PERK-Nrf2-HO-1 信号通路的激活导致铁超载，而 GPX4 的抑制则进一步使癌细胞对铁变态反应敏感。此外，分子对接研究表明，pacidusin B 与铁变态反应诱导剂麦拉宁对接在 xCT 的同一个口袋中。这些结果表明，pacidusin B通过诱导ER介导的铁凋亡细胞死亡发挥抗癌作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Natural Products and Bioprospecting CHEMISTRY, MEDICINAL-

CiteScore

8.30

自引率

2.10%

发文量

审稿时长

13 weeks

期刊介绍： Natural Products and Bioprospecting serves as an international forum for essential research on natural products and focuses on, but is not limited to, the following aspects: Natural products: isolation and structure elucidation Natural products: synthesis Biological evaluation of biologically active natural products Bioorganic and medicinal chemistry Biosynthesis and microbiological transformation Fermentation and plant tissue cultures Bioprospecting of natural products from natural resources All research articles published in this journal have undergone rigorous peer review. In addition to original research articles, Natural Products and Bioprospecting publishes reviews and short communications, aiming to rapidly disseminate the research results of timely interest, and comprehensive reviews of emerging topics in all the areas of natural products. It is also an open access journal, which provides free access to its articles to anyone, anywhere.