Icariin Induces Triple-Negative Breast Cancer Cell Apoptosis and Suppresses Invasion by Inhibiting the JNK/c-Jun Signaling Pathway.

Background: Breast cancer is a common cancer worldwide. Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer characterized by a poor prognosis. Icariin (ICA) is a flavonoid glycoside purified from the natural product Epimedium, which is reported to exert an inhibitory effect on a variety of cancers. However, molecular mechanisms behind ICA suppressed TNBC remain elusive. Methods: The curative effects of ICA on TNBC cells and potential targets were predicted by network pharmacology and molecular biology methods screening, and the mechanism of inhibition was explained through in vitro experiments such as cell function determination, Western blot analysis, molecular docking verification, etc. Results: This study showed that ICA inhibits TNBC cell functions such as proliferation, migration, and invasion in a dose-dependent manner. ICA could induce redox-induced apoptosis in TNBC cell, as shown by ROS upregulation. As a result of network pharmacology, ICA was predicted to be able to inhibit the MAPK signaling pathway. ICA treatment inhibited the expression of JNK and c-Jun and downregulated the antiapoptotic gene cIAP-2. Our results suggested that ICA could induce apoptosis by inducing an excessive accumulation of ROS in cells and suppress TNBC cell invasion via the JNK/c-Jun signaling pathway. Conclusion: We demonstrated that ICA can effectively inhibit cell proliferation and induced apoptosis of TNBC cells. In addition, ICA could inhibit TNBC cell invasion through the JNK/c-Jun signaling pathway. The above suggests that ICA may become a potential drug for TNBC.