Metabolomic profiling of Musanga cecropioides leaf extract reveals cytotoxic mechanisms in MCF-7 breast cancer cells

Breast cancer is a leading cause of cancer-related mortality, necessitating novel therapeutic strategies. This study employed liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics to investigate the cytotoxic effects of Musanga cecropioides leaf extract (MCL) on MCF-7 breast cancer cell lines. Multivariate, univariate and pathway enrichment analyses were conducted to identify significantly altered metabolites and pathways. Rigorous metabolite identification was carried out using authentic standards, the human metabolome database (HMDB) and MS/MS mzCloud database. Following treatment, the orthogonal partial least squares-discriminant analysis (OPLS-DA) showed clear separation and clustering of sample groups with cross-validation values of R 2 Y = 0.998 and Q 2 = 0.992 in the OPLS-DA score plot. Furthermore, multivariate analyses revealed significant metabolic reprogramming, including alterations in glycerophospholipid metabolism, alanine, aspartate, and glutamate metabolism, and the TCA cycle. Ninety-seven (97) metabolites were significantly perturbed, with key changes observed in acetylcholine, phosphocholine, and citric acid levels. Pathway enrichment analysis identified disrupted metabolic pathways critical for cell growth and survival, highlighting potential therapeutic targets. These findings underscore the anticancer potential of MCL extract by modulating metabolic vulnerabilities in breast cancer cells and provide a foundation for further biomarker discovery and therapeutic development. • Untargeted LC-MS metabolomics revealed significant metabolic reprogramming in MCF-7 breast cancer cells treated with Musanga cecropioides leaf extract. • Ninety-seven metabolites were significantly altered, affecting key pathways including glycerophospholipid metabolism, amino acid biosynthesis, and the TCA cycle. • Perturbations in acetylcholine, phosphocholine, and citric acid highlight potential biomarkers and therapeutic targets. • This study provides mechanistic insight into the cytotoxic effects of Musanga cecropioides leaf extract, supporting its relevance in anticancer drug discovery and pharmaceutical development.