Marine Staurosporine Analogues: Activity and Target Identification in Triple-Negative Breast Cancer
2024
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
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.
显示更多 [+] 显示较少 [-]