Cytotoxic Activity of Schisantherin A Against Liver Cancer Cells: In Vitro and In Silico Insights

Objective This study aimed to evaluate the cytotoxic potential of schisantherin A, a bioactive lignan isolated from Schisandra chinensis (Turcz.) Baill., against human liver cancer cell lines through both in vitro and in silico approaches. Methods The cytotoxic activity of schisantherin A was assessed in vitro using three human liver cancer cell lines as HepG2, Hep3B, and Huh7. In silico studies involved molecular docking to evaluate the binding affinity of schisantherin A to two key endoplasmic reticulum stress-related proteins IRE1α and PERK. Molecular dynamics simulations were subsequently performed to assess the stability and interaction profile of the ligand-protein complex. Results Schisantherin A exhibited notable cytotoxicity against the tested liver cancer cells, with IC­ 50 values of 6.65 µM (HepG2), 10.50 µM (Hep3B), and 10.72 µM (Huh7). Molecular docking predicted favorable binding to IRE1α and PERK, with docking scores of −7.6 kcal/mol and −5.5 kcal/mol, respectively. MD simulations revealed a stable binding conformation of schisantherin A within the IRE1α binding pocket, mediated by multiple non-covalent interactions involving key amino acid residues. Conclusion The in vitro and in silico findings suggest that schisantherin A may exert its cytotoxic effects via targeting IRE1α-mediated pathways, supporting its potential as a lead compound for liver cancer therapy.