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Arsenic Trioxide Inhibits Cell Growth and Induces Apoptosis through Inactivation of Notch Signaling Pathway in Breast Cancer

Arsenic trioxide has been reported to inhibit cell growth and induce apoptotic cell death in many human cancer cells including breast cancer. However, the precise molecular mechanisms underlying the anti-tumor activity of arsenic trioxide are still largely unknown. In the present study, we assessed...

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Autores principales: Xia, Jun, Li, Youjian, Yang, Qingling, Mei, Chuanzhong, Chen, Zhiwen, Bao, Bin, Ahmad, Aamir, Miele, Lucio, Sarkar, Fazlul H, Wang, Zhiwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431819/
https://www.ncbi.nlm.nih.gov/pubmed/22949821
http://dx.doi.org/10.3390/ijms13089627
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author Xia, Jun
Li, Youjian
Yang, Qingling
Mei, Chuanzhong
Chen, Zhiwen
Bao, Bin
Ahmad, Aamir
Miele, Lucio
Sarkar, Fazlul H
Wang, Zhiwei
author_facet Xia, Jun
Li, Youjian
Yang, Qingling
Mei, Chuanzhong
Chen, Zhiwen
Bao, Bin
Ahmad, Aamir
Miele, Lucio
Sarkar, Fazlul H
Wang, Zhiwei
author_sort Xia, Jun
collection PubMed
description Arsenic trioxide has been reported to inhibit cell growth and induce apoptotic cell death in many human cancer cells including breast cancer. However, the precise molecular mechanisms underlying the anti-tumor activity of arsenic trioxide are still largely unknown. In the present study, we assessed the effects of arsenic trioxide on cell viability and apoptosis in breast cancer cells. For mechanistic studies, we used multiple cellular and molecular approaches such as MTT assay, apoptosis ELISA assay, gene transfection, RT-PCR, Western blotting, and invasion assays. For the first time, we found a significant reduction in cell viability in arsenic trioxide-treated cells in a dose-dependent manner, which was consistent with induction of apoptosis and also associated with down-regulation of Notch-1 and its target genes. Taken together, our findings provide evidence showing that the down-regulation of Notch-1 by arsenic trioxide could be an effective approach, to cause down-regulation of Bcl-2, and NF-κB, resulting in the inhibition of cell growth and invasion as well as induction of apoptosis. These results suggest that the anti-tumor activity of arsenic trioxide is in part mediated through a novel mechanism involving inactivation of Notch-1 and its target genes. We also suggest that arsenic trioxide could be further developed as a potential therapeutic agent for the treatment of breast cancer.
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spelling pubmed-34318192012-09-04 Arsenic Trioxide Inhibits Cell Growth and Induces Apoptosis through Inactivation of Notch Signaling Pathway in Breast Cancer Xia, Jun Li, Youjian Yang, Qingling Mei, Chuanzhong Chen, Zhiwen Bao, Bin Ahmad, Aamir Miele, Lucio Sarkar, Fazlul H Wang, Zhiwei Int J Mol Sci Article Arsenic trioxide has been reported to inhibit cell growth and induce apoptotic cell death in many human cancer cells including breast cancer. However, the precise molecular mechanisms underlying the anti-tumor activity of arsenic trioxide are still largely unknown. In the present study, we assessed the effects of arsenic trioxide on cell viability and apoptosis in breast cancer cells. For mechanistic studies, we used multiple cellular and molecular approaches such as MTT assay, apoptosis ELISA assay, gene transfection, RT-PCR, Western blotting, and invasion assays. For the first time, we found a significant reduction in cell viability in arsenic trioxide-treated cells in a dose-dependent manner, which was consistent with induction of apoptosis and also associated with down-regulation of Notch-1 and its target genes. Taken together, our findings provide evidence showing that the down-regulation of Notch-1 by arsenic trioxide could be an effective approach, to cause down-regulation of Bcl-2, and NF-κB, resulting in the inhibition of cell growth and invasion as well as induction of apoptosis. These results suggest that the anti-tumor activity of arsenic trioxide is in part mediated through a novel mechanism involving inactivation of Notch-1 and its target genes. We also suggest that arsenic trioxide could be further developed as a potential therapeutic agent for the treatment of breast cancer. Molecular Diversity Preservation International (MDPI) 2012-08-02 /pmc/articles/PMC3431819/ /pubmed/22949821 http://dx.doi.org/10.3390/ijms13089627 Text en © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Xia, Jun
Li, Youjian
Yang, Qingling
Mei, Chuanzhong
Chen, Zhiwen
Bao, Bin
Ahmad, Aamir
Miele, Lucio
Sarkar, Fazlul H
Wang, Zhiwei
Arsenic Trioxide Inhibits Cell Growth and Induces Apoptosis through Inactivation of Notch Signaling Pathway in Breast Cancer
title Arsenic Trioxide Inhibits Cell Growth and Induces Apoptosis through Inactivation of Notch Signaling Pathway in Breast Cancer
title_full Arsenic Trioxide Inhibits Cell Growth and Induces Apoptosis through Inactivation of Notch Signaling Pathway in Breast Cancer
title_fullStr Arsenic Trioxide Inhibits Cell Growth and Induces Apoptosis through Inactivation of Notch Signaling Pathway in Breast Cancer
title_full_unstemmed Arsenic Trioxide Inhibits Cell Growth and Induces Apoptosis through Inactivation of Notch Signaling Pathway in Breast Cancer
title_short Arsenic Trioxide Inhibits Cell Growth and Induces Apoptosis through Inactivation of Notch Signaling Pathway in Breast Cancer
title_sort arsenic trioxide inhibits cell growth and induces apoptosis through inactivation of notch signaling pathway in breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431819/
https://www.ncbi.nlm.nih.gov/pubmed/22949821
http://dx.doi.org/10.3390/ijms13089627
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