Targeting triple-negative breast cancer: apoptotic and antitumor effects of Artemisia sieberi Besser extracts

Artemisia sieberi Besser (A. sieberi) has shown promise as a natural source of safe cytotoxic agents for breast cancer therapy. However, its effects on triple-negative breast cancer (TNBC), a very aggressive subtype lacking targeted treatments, remain poorly studied. This study evaluates the anticancer activity of A. sieberi extracts against the MDA-MB-231 TNBC cell line, comparing results with hormone receptor-positive MCF-7 cells. Aerial parts of A. sieberi were extracted using ethanol and methanol and then chemically characterized via gas chromatography/mass spectrometry (GC/MS) to identify bioactive compounds. Cytotoxic effects were assessed using cell viability assays, while apoptosis induction was examined through flow cytometry (Annexin V/propidium iodide staining), caspase-3/-7 activation assays, and mitochondrial membrane permeabilization visualized using confocal microscopy. Western blotting analyzed the expression levels of apoptotic proteins. In silico molecular docking simulations explored the interactions between phytochemicals and apoptosis-regulating proteins. A. sieberi extracts exhibited higher cytotoxicity against MDA-MB-231 cells than against MCF-7 cells, with lower IC₅₀ values. Treatment of TNBC cells induced apoptosis, evidenced by increased caspase activity, mitochondrial membrane permeabilization, elevated Bax, and decreased Bcl-2 expression. Additionally, colony formation assays demonstrated a significant reduction in tumorigenic potential. Computational analyses indicate that β-sitosterol and stigmasterol, among the main compounds, exhibited strong interactions with apoptosis regulators by docking with Bcl-2, supporting their promising anticancer potential. A. sieberi extracts induce potent apoptosis and exert anti-tumour effects in TNBC cells, highlighting their potential as sources of novel anticancer agents. Further isolation and characterization of active constituents are warranted for therapeutic development.