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。