Introduction

Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis and limited therapeutic options. Fangchinoline, a bisbenzylisoquinoline alkaloid, has demonstrated anticancer activity; however, its molecular mechanism in TNBC remains unclear. This study aimed to investigate the anticancer effects of fangchinoline and explore its potential molecular mechanisms in TNBC.

Material and methods

An integrated in vitro and in silico approach was employed. Molecular docking and molecular dynamics simulations were conducted to evaluate the interaction of fangchinoline with TGF-β1 and mTOR proteins. Cytotoxicity was assessed in murine 4T1 TNBC cells. Flow cytometry was used to analyse cell cycle distribution, apoptosis, and protein expression related to the PI3K/Akt/mTOR pathway and p53.

Results

Fangchinoline demonstrated strong binding affinity toward TGF-β1 and exhibited selective cytotoxicity against 4T1 cells (IC₅₀ = 25.95 µM). Treatment induced apoptosis and mild G2/M phase arrest. In addition, changes in the expression of PI3K, Akt, mTOR, and p53 proteins were observed. These findings suggest that fangchinoline may suppress cell proliferation and promote apoptosis, possibly through modulation of the PI3K/Akt/mTOR signalling pathway; however, this interpretation is based on protein expression data without phosphorylation analysis or functional validation.

Conclusions

Fangchinoline exhibits potential anticancer activity against TNBC cells by inducing apoptosis and affecting key survival-related pathways. Further studies are required to confirm its molecular mechanisms and therapeutic potential.