Cytotoxic and Apoptosis-Associated Activity of Schefflera elliptica (Blume) Harms Ethanolic Extract in T47D Breast Cancer Cells Supported by LC-HRMS Profiling and Molecular Docking

Abstract

Breast cancer continues to impose a substantial global health burden, and natural products remain an important source of candidates for anticancer research. This study investigated the cytotoxic and apoptosis-associated effects of the ethanolic extract of Schefflera elliptica against T47D human breast cancer cells. Cytotoxicity was evaluated using the MTT assay, while apoptosis-associated responses were assessed by Annexin V-FITC/propidium iodide flow cytometry and caspase-3 and caspase-8 immunofluorescence. Metabolite profiling was performed using liquid chromatography–high-resolution mass spectrometry (LC-HRMS), followed by exploratory molecular docking of selected metabolites against the anti-apoptotic protein Bcl-2. The crude ethanolic extract exhibited moderate cytotoxic activity, with an IC50 of 339 μg/mL. Treatment increased the Annexin V-positive cell population, with significant increases observed at 160 and 320 μg/mL, and was accompanied by increased caspase-3 and caspase-8 immunofluorescence signals. LC-HRMS profiling yielded 39 putatively annotated metabolites, with choline, L-norleucine, and valine among the most abundant. Molecular docking predicted interactions of these metabolites within the Bcl-2 binding pocket, although their predicted binding affinities were weaker than those of venetoclax. Overall, the findings indicate that S. elliptica ethanolic extract exhibits moderate cytotoxic activity accompanied by apoptosis-associated cellular responses in T47D cells. The integrated biological, metabolomic, and computational findings provide a basis for further bioactivity-guided investigation of the active constituents and their underlying mechanisms.