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Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential
Cucurbitacin B (CuB) is a widely available triterpenoid molecule that exhibits various biological activities. Previous studies on the anti-tumour mechanism of CuB have mostly focused on cell apoptosis, and research on the ferroptosis-inducing effect has rarely been reported. Herein, we first discove...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933245/ https://www.ncbi.nlm.nih.gov/pubmed/33664249 http://dx.doi.org/10.1038/s41419-021-03516-y |
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author | Huang, Shuai Cao, Bihui Zhang, Jinling Feng, Yunfei Wang, Lu Chen, Xiaopei Su, Hang Liao, Shengrong Liu, Jinggong Yan, Jun Liang, Baoxia |
author_facet | Huang, Shuai Cao, Bihui Zhang, Jinling Feng, Yunfei Wang, Lu Chen, Xiaopei Su, Hang Liao, Shengrong Liu, Jinggong Yan, Jun Liang, Baoxia |
author_sort | Huang, Shuai |
collection | PubMed |
description | Cucurbitacin B (CuB) is a widely available triterpenoid molecule that exhibits various biological activities. Previous studies on the anti-tumour mechanism of CuB have mostly focused on cell apoptosis, and research on the ferroptosis-inducing effect has rarely been reported. Herein, we first discovered the excellent cytotoxicity of CuB towards human nasopharyngeal carcinoma cells and elucidated its potential ferroptosis-inducing mechanisms. Morphology alterations of mitochondrial ultrastructure, as observed via transmission electron microscopy, showed that CuB-treated cells undergo ferroptosis. CuB caused intracellular accumulation of iron ions and depletion of glutathione. Detailed molecular mechanism investigation confirmed that CuB both induced widespread lipid peroxidation and downregulated the expression of GPX4, ultimately initiating a multipronged mechanism of ferroptosis. Furthermore, CuB exhibited anti-tumour effects in vitro by inhibiting cellular microtubule polymerization, arresting cell cycle and suppressing migration and invasion. Finally, CuB significantly inhibited tumour progression without causing obvious side effects in vivo. Altogether, our study highlighted the therapeutic potential of CuB as a ferroptosis-inducing agent for nasopharyngeal cancer, and it provided valuable insights for developing effective anti-tumour agents with novel molecular mechanisms derived from natural products. |
format | Online Article Text |
id | pubmed-7933245 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79332452021-03-19 Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential Huang, Shuai Cao, Bihui Zhang, Jinling Feng, Yunfei Wang, Lu Chen, Xiaopei Su, Hang Liao, Shengrong Liu, Jinggong Yan, Jun Liang, Baoxia Cell Death Dis Article Cucurbitacin B (CuB) is a widely available triterpenoid molecule that exhibits various biological activities. Previous studies on the anti-tumour mechanism of CuB have mostly focused on cell apoptosis, and research on the ferroptosis-inducing effect has rarely been reported. Herein, we first discovered the excellent cytotoxicity of CuB towards human nasopharyngeal carcinoma cells and elucidated its potential ferroptosis-inducing mechanisms. Morphology alterations of mitochondrial ultrastructure, as observed via transmission electron microscopy, showed that CuB-treated cells undergo ferroptosis. CuB caused intracellular accumulation of iron ions and depletion of glutathione. Detailed molecular mechanism investigation confirmed that CuB both induced widespread lipid peroxidation and downregulated the expression of GPX4, ultimately initiating a multipronged mechanism of ferroptosis. Furthermore, CuB exhibited anti-tumour effects in vitro by inhibiting cellular microtubule polymerization, arresting cell cycle and suppressing migration and invasion. Finally, CuB significantly inhibited tumour progression without causing obvious side effects in vivo. Altogether, our study highlighted the therapeutic potential of CuB as a ferroptosis-inducing agent for nasopharyngeal cancer, and it provided valuable insights for developing effective anti-tumour agents with novel molecular mechanisms derived from natural products. Nature Publishing Group UK 2021-03-04 /pmc/articles/PMC7933245/ /pubmed/33664249 http://dx.doi.org/10.1038/s41419-021-03516-y Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Huang, Shuai Cao, Bihui Zhang, Jinling Feng, Yunfei Wang, Lu Chen, Xiaopei Su, Hang Liao, Shengrong Liu, Jinggong Yan, Jun Liang, Baoxia Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential |
title | Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential |
title_full | Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential |
title_fullStr | Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential |
title_full_unstemmed | Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential |
title_short | Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential |
title_sort | induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin b: molecular mechanism and therapeutic potential |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933245/ https://www.ncbi.nlm.nih.gov/pubmed/33664249 http://dx.doi.org/10.1038/s41419-021-03516-y |
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