Drug Design, Development and Therapy (Mar 2023)
Icariin Induces Triple-Negative Breast Cancer Cell Apoptosis and Suppresses Invasion by Inhibiting the JNK/c-Jun Signaling Pathway
Abstract
Shenghan Gao,1,2 Xinyu Zhang,1,2 Jie Liu,3 Fuqing Ji,2 Zhihao Zhang,2 Qingjie Meng,2 Qi Zhang,1 Xiaogang Han,2 He Wu,2 Yulong Yin,2 Yonggang Lv,2 Wenzhen Shi3 1The College of Life Sciences, Northwest University, Xi’an, 710069 People’s Republic of China; 2Department of Thyroid Breast Surgery, Xi’an NO.3 Hospital, the Affiliated Hospital of Northwest University, Xi’an, People’s Republic of China; 3Clinical Medical Center, Xi’an NO.3 Hospital, the Affiliated Hospital of Northwest University, Xi’an, People’s Republic of ChinaCorrespondence: Yonggang Lv, Department of Thyroid Breast Surgery, Xi’an NO.3 Hospital, the Affiliated Hospital of Northwest University, Xi’an, People’s Republic of China, Email [email protected] Wenzhen Shi, Xi’an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi’an No.3 Hospital, The Affiliated Hospital of Northwest University, School of Life Sciences and Medicine, Northwest University, Xi’an, People’s Republic of China, Tel +8615037916770, Email [email protected]: 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.Keywords: triple-negative breast cancer, icariin, JNK/c-Jun, apoptosis, ROS, invasion
