Network Pharmacology, Apoptosis, and Cell Cycle Inhibition of Sesquiterpene Compounds From Qusthul Hindi Root Extract (Saussurea Lappa) in Breast Cancer: An in Silico and in Vitro Approach

Abstract

Objective: The objective of this study was to evaluate the potential and mechanisms of compounds in Qusthul Hindi extract in inhibiting proliferation, cell cycle, and inducing cell death in breast cancer through a network pharmacology approach, in silico validation, and in vitro experiments. Methods: This research employed a literature review approach to identify anti-cancer compounds and utilized a network pharmacology approach to predict the mechanisms of action of the compounds. Insilico docking was performed on the HER2 receptor (PDB: 3PP0) using Molegro Virtual Docker 6.0. Furthermore, the MTT method was used to evaluate the cytotoxic effects of Qusthul Hindi extract on T47D cells, and Flow cytometry was employed to determine the effects of the extract on apoptosis and cell cycle. Results: The network pharmacology analysis revealed that Qusthul Hindi interacted with 66 genes related to breast cancer. Pathway analysis showed a close association between Qusthul Hindi and important signaling pathways such as P53, MAPK, PI3K-Akt, and the cell cycle. Molecular docking results showed better affinity of Saussureamine B and C towards the HER2 receptor compared to trastuzumab. In vitro cytotoxicity assays demonstrated the potential activity of Qusthul Hindi extract against T47D cells (IC50: 32.81 µg/ml). Qusthul Hindi also effectively induced apoptosis in breast cancer cells with a high percentage (85.3%), and inhibited the cell cycle by reducing the G2-M and S phases. Statistical analysis revealed significant differences between the Qusthul Hindi treatment group and the control group in terms of apoptotic cell count (p<0.001). Conclusion: These findings suggest that Qusthul Hindi has potential for development as an anti-cancer agent through the inhibition of proliferation, induction of apoptosis, and cell cycle inhibition in breast cancer.