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