<em>In Vitro</em> Antiproliferative Activity and Selective Cytotoxicity of Sixteen South African <em>Euphorbia</em> Species Against Breast Cancer and Normal Cell Lines

The use of medicinal plants in traditional healthcare systems has a long history, particularly in regions with limited access to modern medical facilities. In South Africa, indigenous knowledge of plant-based remedies has been preserved through oral traditions, making these plants vital resources for local communities. This study investigates sixteen unexplored Euphorbia species for their potential in inhibiting breast cancer cell growth. Due to the small size of the plants, the entire plant was used for each species. A systematic approach was employed, including plant selection, sequential extraction using organic solvents, phytochemical screening, and in vitro cytotoxicity testing using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. High-performance liquid chromatography (HPLC) was used to identify primary metabolites. All sixteen species contained glycosides and triterpenoids. The ethyl acetate (EtOAc) extract of Euphorbia ledienii, dichloromethane (DCM) extract of Euphorbia cooperi, and DCM extract of Euphorbia clavarioides exhibited the highest inhibitory effects on Michigan Cancer Foundation-7 (MCF-7), and M.D. Anderson-Metastatic Breast-231 (MDA-MB-231) cell lines, with cytotoxic concentration (CC₅₀) values of 0.06 μg/mL, 0.07 μg/mL, and 0.23 μg/mL, respectively. Euphorbia tirucalli (DCM extract) and Euphorbia cooperi (hexane extract) displayed selectivity for MDA-MB231 cells, with selectivity index (SI) values of 49.40 and 84.03, respectively. Euphorbia trigona, Euphorbia gorgonis, Euphorbia ledienii, and Euphorbia arabica had similar distribution of secondary metabolites based on HPLC analysis. These findings suggest that certain Euphorbia species exhibit selective cytotoxicity against breast cancer cells while sparing normal cells, highlighting their potential for breast cancer therapy.