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女性健康。目前乳腺癌靶向药物仍然匮乏。天然产物因其低毒、高效而成为乳腺癌靶向药物的主要来源。升麻苷是从升麻中分离纯化的天然化合物，已被建议用于乳腺癌治疗，但其作用机制尚未阐明。在这篇文章中，Cimigenoside 对乳腺癌的抗肿瘤潜力进行了体外和体内研究。此外，我们还通过分子对接研究进一步预测了升麻皂苷与γ-分泌酶可能的结合模式。结果表明，升麻苷通过抑制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。从作用机制来看，Cimigenoside可以抑制γ-分泌酶催化亚基PSEN-1的激活，并通过裂解PSEN-1介导的Notch蛋白。总体而言，我们的研究结果为利用升麻苷作为 BC 临床治疗的有效靶向药物提供了科学支持。