Breast cancer (BC) occurrence and development tremendously affect female health. Currently breast cancer targeted drugs are still scarce. Natural products have become the main source of targeted drug for breast cancer due to low toxicity and high efficiency. Cimigenoside, natural compound isolated and purified from Cimicifuga dahurica (Turcz.) Maxim has been suggested to utilize for breast cancer treatment, however the mechanism of action has not been elucidated yet. In this article, the antitumor potential of Cimigenoside against breast cancer in vitro and in vivo study. Moreover, we further predicted the possible binding mode of Cimigenoside with γ-secretase through molecular docking studies. The results show that Cimigenoside has a significant inhibitory effect towards the proliferation or metastasis of breast cancer cells via suppressing the Notch signaling pathway-mediated mitochondrial apoptosis and EMT (epithelial mesenchymal transition). In terms of mechanism, Cimigenoside could inhibit the activation of PSEN-1, the catalytic subunit of γ-secretase, and also by cleaving the Notch protein mediated by PSEN-1. Overall, our findings provide scientific support to utilize Cimigenoside as an effective targeted drug for clinical treatment of BC.

乳腺癌（BC）的发生和发展极大地影响着女性的健康。目前乳腺癌靶向药物仍然稀缺。天然产物以其低毒、高效等优点成为乳腺癌靶向药物的主要来源。从Cimicifuga dahurica中分离纯化的天然化合物Cimigenoside(Turcz.) Maxim 已被建议用于乳腺癌治疗，但其作用机制尚未阐明。在本文中，西米吉诺苷对乳腺癌的体外和体内抗肿瘤潜力研究。此外，我们通过分子对接研究进一步预测了西米吉诺苷与γ-分泌酶的可能结合模式。结果表明，西米吉诺苷通过抑制Notch信号通路介导的线粒体凋亡和EMT（上皮间质转化），对乳腺癌细胞的增殖或转移具有显着的抑制作用。就机制而言，西米吉诺苷可以抑制PSEN-1（γ-分泌酶的催化亚基）的活化，也可以通过切割PSEN-1介导的Notch蛋白。全面的，