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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...

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Autores principales: Li, Xiaorui, Wang, Shisheng, Deng, Ning, Guo, Xiangyu, Fu, Meiyi, Ma, Yiwen, Sun, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
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.
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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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