A Pyrone Glucoside from Maerua angolensis Induces Caspase-Dependent Apoptosis and Targets AKT1, PARP-1, and Caspase-7 in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is an aggressive subtype lacking effective targeted therapies, highlighting the need for new anticancer agents. Natural products remain a valuable source of bioactive compounds with diverse mechanisms of action. In this study, a pyrone glucoside, 7-hydroxymaltol-3-O-β-D-glucoside, was isolated from the methanolic leaf extract of Maerua angolensis and evaluated for its anticancer activity against TNBC cells. Structural elucidation was achieved using NMR and LC–MS analyses. Both the crude extract and the isolated compound exhibited dose-dependent cytotoxicity against MDA-MB-468 cells, with IC50 values of 2.94 and 0.78 µg/mL, respectively, while showing reduced toxicity toward MCF10A normal cells. Mechanistic studies revealed induction of apoptosis, evidenced by activation of caspase-9 and caspase-7 and PARP cleavage. Confocal imaging further demonstrated lysosomal disruption and nuclear morphological alterations consistent with stress-associated cell death. Gene expression analysis indicated minimal involvement of the PI3K/AKT/mTOR pathway. Molecular docking showed favorable binding of the compound to AKT1, PARP-1, and caspase-7, suggesting a multi-target mode of action. ADMET analysis indicated low oral bioavailability but a favorable safety profile. These findings highlight the potential of this compound as a lead for TNBC therapy.