Investigation of the selective cytotoxic effect of Lamium purpureum extracts on MCF-7 breast cancer cells

Objective: This study aims to evaluate the selective cytotoxicity and underlying cell death mechanisms of Lamium purpureum extract/fractions against MCF-7 luminal A breast cancer cells in comparison to normal mammary epithelial cells.Materials and Methods: The cytotoxicity of five different extract/fractions of Lamium purpureum on MCF-7 breast cancer andHME1 mammary epithelial cells was assessed using the Cell Counting Kit-8 (CCK-8) assay. The most selective fraction was furtherinvestigated via JC-1 mitochondrial membrane potential (MMP) analysis and Annexin V/Propidium Iodide (PI) double staining todetermine the precise mode of cell death.Results: The Lamium purpureum n-hexane (LPH) fraction showed the highest cytotoxicity against MCF-7 cells (IC50 = 30.41 μg/mL)with a favorable selectivity index (SI) of 1.39. Mechanistic assays revealed that LPH did not induce mitochondrial depolarization inMCF-7 cells. Annexin V/PI staining confirmed a dose-dependent induction of primary necrotic cell death. This membrane collapse isconsistent with the lipid-based bioactive constituents of Lamium purpureum.Conclusion: The LPH fraction acts as a selective cytotoxic agent that bypasses classical mitochondrial apoptosis in MCF-7 cells, therebyexecuting a dominant necrotic cell death pathway.