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N-((1-(4-氟苯基)-1H-1,2,3-三唑-4-基)甲基)-2-亚甲基-3-氧代-齐墩烷-12-烯-28-酰胺通过刺激氧化应激和抑制 Notch-Akt 信号通路诱导人乳腺癌细胞凋亡。

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.

机构信息

Cancer Hospital of Dalian University of Technology Liaoning Cancer Hospital & Institute, Shenyang, China.

College of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China.

出版信息

Oxid Med Cell Longev. 2022 Apr 27;2022:8123120. doi: 10.1155/2022/8123120. eCollection 2022.

DOI:10.1155/2022/8123120
PMID:35528507
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9068303/
Abstract

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.

摘要

乳腺癌是癌症相关死亡的主要原因之一，也是全球女性最常见的癌症。尽管乳腺癌治疗取得了进展，但由于新出现或继发耐药，该疾病最终在大多数患者中进展。因此，发现具有高效低毒的新型全身治疗药物至关重要。在这项研究中，我们研究了一种新的齐墩果酸衍生物 N-((1-(4-氟苯基)-1H-1,2,3-三唑-4-基)甲基)-2-亚甲基-3-氧代-齐墩果烷-12-烯-28-酰胺 (ZQL-4c) 是否对乳腺癌具有潜在的抗癌作用。我们发现 ZQL-4c 强烈抑制乳腺癌细胞的增殖和侵袭，并诱导 G2/M 期阻滞和细胞凋亡。然后我们发现 ZQL-4c 诱导活性氧 (ROS) 的产生。然后我们发现 ZQL-4c 显著抑制与氧化应激相关的 Notch-AKT 信号通路。总之，这项研究首次表明，ZQL-4c 通过阻断 Notch-Akt 信号通路，主要通过 ROS 介导的氧化应激，显著抑制乳腺癌的生长和侵袭。因此，ZQL-4c 可能被认为是一种新型的、有潜力的治疗乳腺癌的抗癌药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/2921c6cef22a/OMCL2022-8123120.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/be1c034cfb26/OMCL2022-8123120.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/aaa60591c8fd/OMCL2022-8123120.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/dfbdcd9dc57f/OMCL2022-8123120.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/99e77ec184d2/OMCL2022-8123120.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/ed29c0053236/OMCL2022-8123120.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/5068b72bd66f/OMCL2022-8123120.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/96b8949f4d6f/OMCL2022-8123120.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/2921c6cef22a/OMCL2022-8123120.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/be1c034cfb26/OMCL2022-8123120.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/aaa60591c8fd/OMCL2022-8123120.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/dfbdcd9dc57f/OMCL2022-8123120.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/99e77ec184d2/OMCL2022-8123120.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/ed29c0053236/OMCL2022-8123120.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/5068b72bd66f/OMCL2022-8123120.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/96b8949f4d6f/OMCL2022-8123120.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d00/9068303/2921c6cef22a/OMCL2022-8123120.008.jpg

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