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Natural products remain a valuable source of bioactive compounds with diverse mechanisms of action. In this study, a pyrone glucoside, 7-hydroxymaltol-3-O-\u03b2-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\u2013MS 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 \u00b5g\/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.<\/jats:p>","DOI":"10.3390\/biom16060861","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T10:19:53Z","timestamp":1781691593000},"page":"861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Pyrone Glucoside from Maerua angolensis Induces Caspase-Dependent Apoptosis and Targets AKT1, PARP-1, and Caspase-7 in Triple-Negative Breast Cancer"],"prefix":"10.3390","volume":"16","author":[{"given":"Jamila","family":"Aminu","sequence":"first","affiliation":[{"name":"Department of Chemistry, Morgan State University, 1700 E. Cold Spring Lane, Baltimore, MD 21251, USA"},{"name":"Department of Biochemistry, Bayero University, P.M.B. 3011, Gwarzo Road, Kano, Nigeria"},{"name":"Department of Biochemistry, Gombe State University, P.M.B. 127, Tudun Wada, Gombe, Gombe State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amina Jega","family":"Yusuf","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Morgan State University, 1700 E. Cold Spring Lane, Baltimore, MD 21251, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4455-9266","authenticated-orcid":false,"given":"Bor-Jang","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Biology, Morgan State University, 1700 E. 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Cold Spring Lane, Baltimore, MD 21251, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7525-4652","authenticated-orcid":false,"given":"Valerie","family":"Odero-Marah","sequence":"additional","affiliation":[{"name":"Department of Biology, Morgan State University, 1700 E. 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