海洋石杉碱类似物：三阴性乳腺癌的活性和靶点鉴定

IF 4.9 2区医学 Q1 CHEMISTRY, MEDICINAL Marine Drugs Pub Date : 2024-10-05 DOI:10.3390/md22100459

Ru-Yi Chen, Li-Jian Ding, Yan-Jun Liu, Jin-Jin Shi, Jing Yu, Chang-Yun Li, Jian-Fei Lu, Guan-Jun Yang, Jiong Chen

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引用次数: 0

摘要

三阴性乳腺癌（TNBC）是乳腺癌的一种亚型，具有高死亡率和耐药性，目前尚无靶向药物。化合物 4 是一种从海洋海绵中的链霉菌 NBU3142 中提取的石杉碱类生物碱，具有很强的抗 TNBC 活性。这项研究调查了它对 MDA-MB-231 细胞及其耐药变体的影响。研究结果表明，化合物 4 可抑制乳腺癌细胞迁移，诱导细胞凋亡，阻止细胞周期，并促进普通和紫杉醇耐药 MDA-MB-231 细胞的衰老。此外，该研究还发现有丝分裂原活化蛋白激酶激酶 11（MAP3K11）是化合物 4 的靶点，这表明化合物 4 通过影响细胞增殖、迁移和细胞周期的进展，在乳腺肿瘤发生过程中发挥了作用。

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

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 4, a staurosporine alkaloid derived from Streptomyces 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 4 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 4, implicating its role in breast tumorigenesis by affecting cell proliferation, migration, and cell cycle progression.

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来源期刊

Marine Drugs 医学-医药化学

CiteScore

9.60

自引率

14.80%

发文量

671

审稿时长

1 months

期刊介绍： Marine Drugs (ISSN 1660-3397) publishes reviews, regular research papers and short notes on the research, development and production of drugs from the sea. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible, particularly synthetic procedures and characterization information for bioactive compounds. There is no restriction on the length of the experimental section.