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Anomanolide C suppresses tumor progression and metastasis by ubiquitinating GPX4-driven autophagy-dependent ferroptosis in triple negative breast cancer
Anomanolide C (AC), a natural withanolide isolated from Tubocapsicum anomalum, has been reported to have exhibits remarkable anti-tumour activities in several types of human cancers, particularly triple-negative breast cancer (TNBC). However, its intricate mechanisms still remain need to be clarifie...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197885/ https://www.ncbi.nlm.nih.gov/pubmed/37215985 http://dx.doi.org/10.7150/ijbs.82120 |
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author | Chen, Yan-Mei Xu, Wei Liu, Yang Zhang, Jia-Hui Yang, Yuan-Yuan Wang, Zhi-wen Sun, De-Juan Li, Hua Liu, Bo Chen, Li-Xia |
author_facet | Chen, Yan-Mei Xu, Wei Liu, Yang Zhang, Jia-Hui Yang, Yuan-Yuan Wang, Zhi-wen Sun, De-Juan Li, Hua Liu, Bo Chen, Li-Xia |
author_sort | Chen, Yan-Mei |
collection | PubMed |
description | Anomanolide C (AC), a natural withanolide isolated from Tubocapsicum anomalum, has been reported to have exhibits remarkable anti-tumour activities in several types of human cancers, particularly triple-negative breast cancer (TNBC). However, its intricate mechanisms still remain need to be clarified. Here, we evaluated whether AC could inhibit cell proliferation and the role of AC in ferroptosis induction and autophagy activation. Subsequently, the anti-migration potential of AC was found via autophagy-dependent ferroptosis. Additionally, we found that AC reduced the expression of GPX4 by ubiquitination and inhibited TNBC proliferation and metastasis in vitro and in vivo. Moreover, we demonstrated that AC induced autophagy-dependent ferroptosis, and led to Fe(2+) accumulation via ubiquitinating GPX4. Moreover, AC was shown to induce autophagy-dependent ferroptosis as well as to inhibit TNBC proliferation and migration via GPX4 ubiquitination. Together, these results demonstrated that AC inhibited the progression and metastasis of TNBC by inducing autophagy-dependent ferroptosis via ubiquitinating GPX4, which might shed light on exploiting AC as a new drug candidate for the future TNBC therapy. |
format | Online Article Text |
id | pubmed-10197885 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-101978852023-05-20 Anomanolide C suppresses tumor progression and metastasis by ubiquitinating GPX4-driven autophagy-dependent ferroptosis in triple negative breast cancer Chen, Yan-Mei Xu, Wei Liu, Yang Zhang, Jia-Hui Yang, Yuan-Yuan Wang, Zhi-wen Sun, De-Juan Li, Hua Liu, Bo Chen, Li-Xia Int J Biol Sci Research Paper Anomanolide C (AC), a natural withanolide isolated from Tubocapsicum anomalum, has been reported to have exhibits remarkable anti-tumour activities in several types of human cancers, particularly triple-negative breast cancer (TNBC). However, its intricate mechanisms still remain need to be clarified. Here, we evaluated whether AC could inhibit cell proliferation and the role of AC in ferroptosis induction and autophagy activation. Subsequently, the anti-migration potential of AC was found via autophagy-dependent ferroptosis. Additionally, we found that AC reduced the expression of GPX4 by ubiquitination and inhibited TNBC proliferation and metastasis in vitro and in vivo. Moreover, we demonstrated that AC induced autophagy-dependent ferroptosis, and led to Fe(2+) accumulation via ubiquitinating GPX4. Moreover, AC was shown to induce autophagy-dependent ferroptosis as well as to inhibit TNBC proliferation and migration via GPX4 ubiquitination. Together, these results demonstrated that AC inhibited the progression and metastasis of TNBC by inducing autophagy-dependent ferroptosis via ubiquitinating GPX4, which might shed light on exploiting AC as a new drug candidate for the future TNBC therapy. Ivyspring International Publisher 2023-05-08 /pmc/articles/PMC10197885/ /pubmed/37215985 http://dx.doi.org/10.7150/ijbs.82120 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Chen, Yan-Mei Xu, Wei Liu, Yang Zhang, Jia-Hui Yang, Yuan-Yuan Wang, Zhi-wen Sun, De-Juan Li, Hua Liu, Bo Chen, Li-Xia Anomanolide C suppresses tumor progression and metastasis by ubiquitinating GPX4-driven autophagy-dependent ferroptosis in triple negative breast cancer |
title | Anomanolide C suppresses tumor progression and metastasis by ubiquitinating GPX4-driven autophagy-dependent ferroptosis in triple negative breast cancer |
title_full | Anomanolide C suppresses tumor progression and metastasis by ubiquitinating GPX4-driven autophagy-dependent ferroptosis in triple negative breast cancer |
title_fullStr | Anomanolide C suppresses tumor progression and metastasis by ubiquitinating GPX4-driven autophagy-dependent ferroptosis in triple negative breast cancer |
title_full_unstemmed | Anomanolide C suppresses tumor progression and metastasis by ubiquitinating GPX4-driven autophagy-dependent ferroptosis in triple negative breast cancer |
title_short | Anomanolide C suppresses tumor progression and metastasis by ubiquitinating GPX4-driven autophagy-dependent ferroptosis in triple negative breast cancer |
title_sort | anomanolide c suppresses tumor progression and metastasis by ubiquitinating gpx4-driven autophagy-dependent ferroptosis in triple negative breast cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197885/ https://www.ncbi.nlm.nih.gov/pubmed/37215985 http://dx.doi.org/10.7150/ijbs.82120 |
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