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N-((1-(4-Fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-methylene-3-oxo-olean-12-en-28-amide Induces Apoptosis in Human Breast Cancer Cells by Stimulating Oxidative Stress and Inhibiting the Notch-Akt Signaling Pathway
Breast cancer is of the leading causes of cancer-related deaths and the most frequently diagnosed cancer among females worldwide. Despite advancements in breast cancer therapy, the disease eventually progresses in most patients because of de novo or secondary resistance. Thus, discovering novel drug...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068303/ https://www.ncbi.nlm.nih.gov/pubmed/35528507 http://dx.doi.org/10.1155/2022/8123120 |
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author | Li, Xiaorui Wang, Shisheng Deng, Ning Guo, Xiangyu Fu, Meiyi Ma, Yiwen Sun, Tao |
author_facet | Li, Xiaorui Wang, Shisheng Deng, Ning Guo, Xiangyu Fu, Meiyi Ma, Yiwen Sun, Tao |
author_sort | Li, Xiaorui |
collection | PubMed |
description | Breast cancer is of the leading causes of cancer-related deaths and the most frequently diagnosed cancer among females worldwide. Despite advancements in breast cancer therapy, the disease eventually progresses in most patients because of de novo or secondary resistance. Thus, discovering novel drugs with high effectiveness and low toxicity for systemic therapy is essential. In this study, we investigated whether a new oleanolic derivative N-((1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-methylene-3-oxo-olean-12-en-28-amide (ZQL-4c) exhibits potential anticancer effects against breast cancer. We determined that ZQL-4c strongly inhibited cell proliferation and invasion and induced G2/M phase arrest and apoptosis in breast cancer cells. We then found that ZQL-4c induced the production of reactive oxygen species (ROS). We then found that ZQL-4c significantly inhibited Notch-AKT signaling pathways that are related to oxidative stress. Taken together, this study is the first to show that ZQL-4c can significantly suppress the growth and invasion of breast cancer by blocking Notch-Akt signaling pathways, which are mainly regulated by ROS-mediated oxidative stress. Thus, ZQL-4c might be considered a novel and potential anticancer drug for breast cancer treatment. |
format | Online Article Text |
id | pubmed-9068303 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-90683032022-05-05 N-((1-(4-Fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-methylene-3-oxo-olean-12-en-28-amide Induces Apoptosis in Human Breast Cancer Cells by Stimulating Oxidative Stress and Inhibiting the Notch-Akt Signaling Pathway Li, Xiaorui Wang, Shisheng Deng, Ning Guo, Xiangyu Fu, Meiyi Ma, Yiwen Sun, Tao Oxid Med Cell Longev Research Article Breast cancer is of the leading causes of cancer-related deaths and the most frequently diagnosed cancer among females worldwide. Despite advancements in breast cancer therapy, the disease eventually progresses in most patients because of de novo or secondary resistance. Thus, discovering novel drugs with high effectiveness and low toxicity for systemic therapy is essential. In this study, we investigated whether a new oleanolic derivative N-((1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-methylene-3-oxo-olean-12-en-28-amide (ZQL-4c) exhibits potential anticancer effects against breast cancer. We determined that ZQL-4c strongly inhibited cell proliferation and invasion and induced G2/M phase arrest and apoptosis in breast cancer cells. We then found that ZQL-4c induced the production of reactive oxygen species (ROS). We then found that ZQL-4c significantly inhibited Notch-AKT signaling pathways that are related to oxidative stress. Taken together, this study is the first to show that ZQL-4c can significantly suppress the growth and invasion of breast cancer by blocking Notch-Akt signaling pathways, which are mainly regulated by ROS-mediated oxidative stress. Thus, ZQL-4c might be considered a novel and potential anticancer drug for breast cancer treatment. Hindawi 2022-04-27 /pmc/articles/PMC9068303/ /pubmed/35528507 http://dx.doi.org/10.1155/2022/8123120 Text en Copyright © 2022 Xiaorui Li et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Li, Xiaorui Wang, Shisheng Deng, Ning Guo, Xiangyu Fu, Meiyi Ma, Yiwen Sun, Tao N-((1-(4-Fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-methylene-3-oxo-olean-12-en-28-amide Induces Apoptosis in Human Breast Cancer Cells by Stimulating Oxidative Stress and Inhibiting the Notch-Akt Signaling Pathway |
title | N-((1-(4-Fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-methylene-3-oxo-olean-12-en-28-amide Induces Apoptosis in Human Breast Cancer Cells by Stimulating Oxidative Stress and Inhibiting the Notch-Akt Signaling Pathway |
title_full | N-((1-(4-Fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-methylene-3-oxo-olean-12-en-28-amide Induces Apoptosis in Human Breast Cancer Cells by Stimulating Oxidative Stress and Inhibiting the Notch-Akt Signaling Pathway |
title_fullStr | N-((1-(4-Fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-methylene-3-oxo-olean-12-en-28-amide Induces Apoptosis in Human Breast Cancer Cells by Stimulating Oxidative Stress and Inhibiting the Notch-Akt Signaling Pathway |
title_full_unstemmed | N-((1-(4-Fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-methylene-3-oxo-olean-12-en-28-amide Induces Apoptosis in Human Breast Cancer Cells by Stimulating Oxidative Stress and Inhibiting the Notch-Akt Signaling Pathway |
title_short | N-((1-(4-Fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-methylene-3-oxo-olean-12-en-28-amide Induces Apoptosis in Human Breast Cancer Cells by Stimulating Oxidative Stress and Inhibiting the Notch-Akt Signaling Pathway |
title_sort | n-((1-(4-fluorophenyl)-1h-1,2,3-triazol-4-yl)methyl)-2-methylene-3-oxo-olean-12-en-28-amide induces apoptosis in human breast cancer cells by stimulating oxidative stress and inhibiting the notch-akt signaling pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068303/ https://www.ncbi.nlm.nih.gov/pubmed/35528507 http://dx.doi.org/10.1155/2022/8123120 |
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