Revealing the Role of Beesioside O from Actaea vaginata for the Treatment of Breast Cancer Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation

Breast cancer remains a leading cause of malignancy-related mortality among women, with rising global incidence. While surgical intervention is effective for early-stage breast cancer, drug therapy is indispensable, particularly for triple-negative breast cancer, where treatment options are still limited. <i>Actaea vaginata</i>, a traditional Chinese medicinal herb, has been historically applied for inflammatory conditions, including pharyngitis and stomatitis. However, its antitumor potential remains under-reported. In this study, a cycloartane triterpene saponin, beesioside O (BO), was isolated from this plant. Its antitumor activity was evaluated in vitro. Its potential therapeutic mechanisms were elucidated through network pharmacology. BO exhibited substantial potency in inhibiting breast cancer cells. Network pharmacology analysis uncovered 179 potential pharmacological targets of BO, which were predominantly concentrated in pathways, such as pathways in cancer, the PI3K-Akt signaling pathway, and chemical carcinogenesis receptor activation. Molecular docking analysis indicated that STAT3 exhibited minimal binding energy with BO. Additionally, molecular dynamics simulations verified the conformational stability of the BO-STAT3 complex. Western blot analysis demonstrated that STAT3 was downregulated following administration. These results imply that BO may exhibit a multi-target, synergistic therapeutic effect against breast cancer, with STAT3 recognized as a pivotal target. This study demonstrates the potential of BO for development as a chemotherapeutic agent for breast cancer treatment. It lays the groundwork for further exploration of BO's bioactivity and provides valuable insights into its molecular mechanisms in breast cancer therapy.