Ursodeoxycholic acid prompts glycolytic dominance, reductive stress and epithelial-to-mesenchymal transition in ovarian cancer cells through NRF2 activation.

IF 6.1 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-04-03 DOI:10.1038/s41420-025-02398-9

Adrienn Sipos, Éva Kerekes, Dóra Szeőcs, Fanni Szarvas, Szandra Schwarcz, Emese Tóth, Gyula Ujlaki, Edit Mikó, Peter Bai

{"title":"Ursodeoxycholic acid prompts glycolytic dominance, reductive stress and epithelial-to-mesenchymal transition in ovarian cancer cells through NRF2 activation.","authors":"Adrienn Sipos, Éva Kerekes, Dóra Szeőcs, Fanni Szarvas, Szandra Schwarcz, Emese Tóth, Gyula Ujlaki, Edit Mikó, Peter Bai","doi":"10.1038/s41420-025-02398-9","DOIUrl":null,"url":null,"abstract":"<p><p>Numerous secreted bacterial metabolites were identified with bioactivity in various neoplasias, including ovarian cancer. One such metabolite is ursodeoxycholic acid (UDCA), a secondary bile acid that has widespread beneficial effects in neoplasias. Hereby, we assessed the bioactivity of UDCA in cell models of ovarian cancer, by applying UDCA in concentrations corresponding to the serum reference concentrations of UDCA (300 nM). UDCA induced epithelial-to-mesenchymal transition (EMT), increased the flux of glycolysis and reduced the naturally occurring oxidative stress in ovarian cancer cells. These changes were dependent on the activation of NRF2. The tumoral overexpression of UDCA-induced genes in humans correlated with worse survival. These results point out that bacterial metabolites may have opposite effects in different neoplasias and raise the possibility that UDCA-containing remedies on the long run may support cancer progression in ovarian cancer patients.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"134"},"PeriodicalIF":6.1000,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965337/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41420-025-02398-9","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Numerous secreted bacterial metabolites were identified with bioactivity in various neoplasias, including ovarian cancer. One such metabolite is ursodeoxycholic acid (UDCA), a secondary bile acid that has widespread beneficial effects in neoplasias. Hereby, we assessed the bioactivity of UDCA in cell models of ovarian cancer, by applying UDCA in concentrations corresponding to the serum reference concentrations of UDCA (300 nM). UDCA induced epithelial-to-mesenchymal transition (EMT), increased the flux of glycolysis and reduced the naturally occurring oxidative stress in ovarian cancer cells. These changes were dependent on the activation of NRF2. The tumoral overexpression of UDCA-induced genes in humans correlated with worse survival. These results point out that bacterial metabolites may have opposite effects in different neoplasias and raise the possibility that UDCA-containing remedies on the long run may support cancer progression in ovarian cancer patients.

查看原文本刊更多论文

熊去氧胆酸通过NRF2激活促进卵巢癌细胞糖酵解优势、还原性应激和上皮向间质转化。

许多分泌的细菌代谢物在包括卵巢癌在内的各种肿瘤中被鉴定出具有生物活性。其中一种代谢物是熊去氧胆酸（UDCA），这是一种次生胆汁酸，对肿瘤有广泛的有益作用。因此，我们通过将UDCA应用于与UDCA血清参考浓度（300 nM）相对应的浓度，来评估UDCA在卵巢癌细胞模型中的生物活性。UDCA诱导卵巢癌细胞上皮-间质转化（EMT），增加糖酵解通量，减少自然发生的氧化应激。这些变化依赖于NRF2的激活。人类肿瘤中udca诱导基因的过表达与较差的生存率相关。这些结果指出，细菌代谢物可能在不同的肿瘤中具有相反的作用，并提高了含有udca的药物从长远来看可能支持卵巢癌患者癌症进展的可能性。

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

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.