Key results
Icariin selectively inhibited proliferation and triggered apoptosis in TNBC cells in a concentration- and time-dependent manner, but exhibited little cytotoxicity in normal breast cells. Moreover, icariin induced cell apoptosis via a mitochondria-mediated pathway, as indicated by upregulated ratio of Bax/Bcl-2 and ROS induction. Importantly, icariin impaired activation of NF-κB/EMT pathway by upregulating expression of SIRT6, resulting in inhibition of migration and invasion of breast cancer cells. Additionally, oss-128167, an inhibitor of SIRT6, dramatically attenuated anti-migration and anti-invasion effects of icariin. Notably, icariin exhibited a significant tumor growth inhibition and anti-pulmonary metastasis effect in a tumor mouse model of MDA-MB-231 and 4T1 cells by regulating tumor immunosuppressive microenvironment.