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Compound 4, a staurosporine alkaloid from Streptomyces sp. NBU3142 isolated in a marine sponge, shows potent anti-TNBC effects in MDA-MB-231 cells and their drug-resistant variants. The compound suppresses migration, triggers apoptosis, induces cell-cycle arrest, and promotes cellular senescence in both sensitive and paclitaxel-resistant models. 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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) asa target of compound 4, implicating its role in breast tumorigenesis by affecting cell proliferation, migration, and cell cycle progression.  \nCitation: Chen, R.-Y.; Ding, L.-J.; Liu, Y.-J.; Shi, J.-J.; Yu, J.; Li, C.-Y.; Lu, J.-F.; Yang, G.-J.; Chen, J. Marine Staurosporine Analogues: Activity and Target Identification in  \nTriple-Negative Breast Cancer. Mar. Drugs 2024, 22, 459. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/md22100459](10.3390/md22100459)  \nAcademic Editor: Masaaki Tamura  \nReceived: 24 August 2024  \nRevised: 28 September 2024  \nAccepted: 3 October 2024  \nPublished: 5 October 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nKeywords: staurosporine analogue; apoptosis; triple-negative breast cancer; cancer stem cells; cell migration; MAP3K11  \n1. Introduction  \nBreast cancer, the second leading cause of cancer-related deaths in women globally, exhibits considerable heterogeneity, ranging from stem cell-like to differentiated cells [1–3] . Approximately 10–20% of breast cancer cases are triple-negative breast cancer (TNBC), known for its aggressive behavior and lack of targeted therapies [4,5] . This subtype is responsible for a large proportion of deaths in breast cancer patients due to its high metastatic rate and poor prognosis [6,7] . Treatment typically involves surgery, radiotherapy, immunotherapy, or chemotherapy, but the resistance and poor outcomes associated with chemotherapy underscore the need for novel therapeutic targets and drug development [8] .  \nThe ocean possesses a unique environment and rich biodiversity not found in terrestrial habitats, with a diverse array of marine organisms serving as sources of natural products with distinct functions. Marine natural product chemistry has experienced significant growth in the past three decades [9] . Numerous natural products with nov","cbCaic8AUV90CYnH","https://ap.wps.com/l/cbCaic8AUV90CYnH","pdf",4696502,18,"English","# Abstract\n# Introduction\n## Marine natural products as anticancer sources\n## TNBC background and treatment challenges\n## Study rationale and compound evaluation (TNBC cell lines)","[{\"question\":\"What is the main goal of the study on marine staurosporine analogues?\",\"answer\":\"To evaluate the anti-triple-negative breast cancer activity of compound 4 and identify its biological target responsible for the observed effects.\"},{\"question\":\"Which compound and source are used to test anti-TNBC activity?\",\"answer\":\"Compound 4, a staurosporine alkaloid derived from Streptomyces sp. NBU3142 isolated from a marine sponge, is tested on MDA-MB-231 cells and drug-resistant variants.\"},{\"question\":\"What key cellular effects does compound 4 cause in TNBC cells?\",\"answer\":\"Compound 4 inhibits cell migration, induces apoptosis, arrests the cell cycle, and promotes cellular senescence in both regular and paclitaxel-resistant MDA-MB-231 cells.\"}]","Marine Staurosporine Analogues - Activity and Target Identification in Triple-Negative Breast Cancer | PDF",1790023223,45]