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Simvastatin induced ferroptosis for triple-negative breast cancer therapy

Triple-negative breast cancer (TNBC), a management of aggressive breast cancer, remains an unmet medical challenge. Although a wave of efforts had spurred to design novel therapeutic method of TNBC, unpredictable prognosis with lacking effective therapeutic targets along with the resistance to apopt...

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Autores principales: Yao, Xianxian, Xie, Ruihong, Cao, Yongbin, Tang, Jing, Men, Yongzhi, Peng, Haibao, Yang, Wuli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502296/
https://www.ncbi.nlm.nih.gov/pubmed/34627266
http://dx.doi.org/10.1186/s12951-021-01058-1
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author Yao, Xianxian
Xie, Ruihong
Cao, Yongbin
Tang, Jing
Men, Yongzhi
Peng, Haibao
Yang, Wuli
author_facet Yao, Xianxian
Xie, Ruihong
Cao, Yongbin
Tang, Jing
Men, Yongzhi
Peng, Haibao
Yang, Wuli
author_sort Yao, Xianxian
collection PubMed
description Triple-negative breast cancer (TNBC), a management of aggressive breast cancer, remains an unmet medical challenge. Although a wave of efforts had spurred to design novel therapeutic method of TNBC, unpredictable prognosis with lacking effective therapeutic targets along with the resistance to apoptosis seriously limited survival benefits. Ferroptosis is a non-apoptotic form of cell death that is induced by excessive lipid peroxidation, which provide an innovative way to combat cancer. Emerging evidence suggests that ferroptosis plays an important role in the treatment of TNBC cells. Herein, a novel ferroptosis nanomedicine was prepared by loading simvastatin (SIM), a ferroptosis drug, into zwitterionic polymer coated magnetic nanoparticles (Fe(3)O(4)@PCBMA) to improve the therapeutic effect of TNBC. The as-obtained Fe(3)O(4)@PCBMA-SIM nanoparticles demonstrated more cytotoxicity against MDA-MB-231 than MCF-7 due to the higher expression of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), which demonstrated that statins could effectively kill TNBC. Further experiments showed that SIM could inhibit the expression of HMGCR to downregulate the mevalonate (MVA) pathway and glutathione peroxidase 4 (GPX4), thereby inducing cancer cell ferroptosis. What’s more, PCBMA endows Fe(3)O(4)@PCBMA longer blood circulation performance to enhance their accumulation at tumor sites. Given that Fe(3)O(4) have proven for clinical applications by the U.S. Food and Drug Administration (FDA) and SIM could induce cancer cell ferroptosis, the developed Fe(3)O(4)@PCBMA-SIM nanosystem would have great potential in clinics for overcoming the drug resistance brought about by apoptotic drugs to cancer cells. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-01058-1.
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spelling pubmed-85022962021-10-20 Simvastatin induced ferroptosis for triple-negative breast cancer therapy Yao, Xianxian Xie, Ruihong Cao, Yongbin Tang, Jing Men, Yongzhi Peng, Haibao Yang, Wuli J Nanobiotechnology Research Triple-negative breast cancer (TNBC), a management of aggressive breast cancer, remains an unmet medical challenge. Although a wave of efforts had spurred to design novel therapeutic method of TNBC, unpredictable prognosis with lacking effective therapeutic targets along with the resistance to apoptosis seriously limited survival benefits. Ferroptosis is a non-apoptotic form of cell death that is induced by excessive lipid peroxidation, which provide an innovative way to combat cancer. Emerging evidence suggests that ferroptosis plays an important role in the treatment of TNBC cells. Herein, a novel ferroptosis nanomedicine was prepared by loading simvastatin (SIM), a ferroptosis drug, into zwitterionic polymer coated magnetic nanoparticles (Fe(3)O(4)@PCBMA) to improve the therapeutic effect of TNBC. The as-obtained Fe(3)O(4)@PCBMA-SIM nanoparticles demonstrated more cytotoxicity against MDA-MB-231 than MCF-7 due to the higher expression of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), which demonstrated that statins could effectively kill TNBC. Further experiments showed that SIM could inhibit the expression of HMGCR to downregulate the mevalonate (MVA) pathway and glutathione peroxidase 4 (GPX4), thereby inducing cancer cell ferroptosis. What’s more, PCBMA endows Fe(3)O(4)@PCBMA longer blood circulation performance to enhance their accumulation at tumor sites. Given that Fe(3)O(4) have proven for clinical applications by the U.S. Food and Drug Administration (FDA) and SIM could induce cancer cell ferroptosis, the developed Fe(3)O(4)@PCBMA-SIM nanosystem would have great potential in clinics for overcoming the drug resistance brought about by apoptotic drugs to cancer cells. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-01058-1. BioMed Central 2021-10-09 /pmc/articles/PMC8502296/ /pubmed/34627266 http://dx.doi.org/10.1186/s12951-021-01058-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yao, Xianxian
Xie, Ruihong
Cao, Yongbin
Tang, Jing
Men, Yongzhi
Peng, Haibao
Yang, Wuli
Simvastatin induced ferroptosis for triple-negative breast cancer therapy
title Simvastatin induced ferroptosis for triple-negative breast cancer therapy
title_full Simvastatin induced ferroptosis for triple-negative breast cancer therapy
title_fullStr Simvastatin induced ferroptosis for triple-negative breast cancer therapy
title_full_unstemmed Simvastatin induced ferroptosis for triple-negative breast cancer therapy
title_short Simvastatin induced ferroptosis for triple-negative breast cancer therapy
title_sort simvastatin induced ferroptosis for triple-negative breast cancer therapy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502296/
https://www.ncbi.nlm.nih.gov/pubmed/34627266
http://dx.doi.org/10.1186/s12951-021-01058-1
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