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海洋类 Staurosporine 类似物:三阴性乳腺癌中的活性和靶标鉴定。

Marine Staurosporine Analogues: Activity and Target Identification in Triple-Negative Breast Cancer.

机构信息

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, School of Marine Sciences, Ningbo University, Ningbo 315211, China.

School of Pharmacy, Health Science Center, Ningbo University, Ningbo 315211, China.

出版信息

Mar Drugs. 2024 Oct 5;22(10):459. doi: 10.3390/md22100459.

DOI:10.3390/md22100459
PMID:39452867
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11509616/
Abstract

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and drug resistance and no targeted drug available at present. Compound , a staurosporine alkaloid derived from sp. NBU3142 in a marine sponge, exhibits potent anti-TNBC activity. This research investigated its impact on MDA-MB-231 cells and their drug-resistant variants. The findings highlighted that compound inhibits breast cancer cell migration, induces apoptosis, arrests the cell cycle, and promotes cellular senescence in both regular and paclitaxel-resistant MDA-MB-231 cells. Additionally, this study identified mitogen-activated protein kinase kinase kinase 11 (MAP3K11) as a target of compound , implicating its role in breast tumorigenesis by affecting cell proliferation, migration, and cell cycle progression.

摘要

三阴性乳腺癌(TNBC)是一种死亡率高且耐药性强的乳腺癌亚型,目前尚无靶向药物。化合物是一种来源于海洋海绵中的 sp. NBU3142 的新型星形孢菌素生物碱,具有很强的抗 TNBC 活性。本研究探讨了其对 MDA-MB-231 细胞及其耐药变体的影响。研究结果表明,化合物 抑制乳腺癌细胞迁移,诱导细胞凋亡,使细胞周期停滞,并促进正常和紫杉醇耐药的 MDA-MB-231 细胞衰老。此外,本研究还确定丝裂原活化蛋白激酶激酶激酶 11(MAP3K11)是化合物的靶点,表明其通过影响细胞增殖、迁移和细胞周期进程在乳腺癌发生中起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/2464f0440929/marinedrugs-22-00459-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/0030d892e845/marinedrugs-22-00459-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/aa4a2b1df71b/marinedrugs-22-00459-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/9ea6795a0e2e/marinedrugs-22-00459-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/c2aea4b6af20/marinedrugs-22-00459-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/9f02003120be/marinedrugs-22-00459-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/473157291f7f/marinedrugs-22-00459-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/2464f0440929/marinedrugs-22-00459-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/0030d892e845/marinedrugs-22-00459-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/b99ff30afd1c/marinedrugs-22-00459-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/aa4a2b1df71b/marinedrugs-22-00459-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/9ea6795a0e2e/marinedrugs-22-00459-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/c2aea4b6af20/marinedrugs-22-00459-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/9f02003120be/marinedrugs-22-00459-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/473157291f7f/marinedrugs-22-00459-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7042/11509616/2464f0440929/marinedrugs-22-00459-g008.jpg

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