HPLC-ESI-QTOF-MS/MS-Guided Profiling of Bioactive Compounds in Fresh and Stored Saffron Corms Reveals Potent Anticancer Activity Against Colorectal Cancer Baddaoui, Sanae Saalaoui, Ennouamane Khibech, Oussama Salagre Simón, Diego Fernández Ochoa, Álvaro Mamri, Samira Aktary, Nahida Rahman, Muntajin Rani, Amama Asehraou, Abdeslam Kim, Bonglee Agil Abdalla, Mhmad Ahmad Crocus sativus Corms Anthraquinones Background: Saffron (Crocus sativus L.) corms, often discarded as agricultural by-products, are a promising and sustainable source of bioactive metabolites with potential therapeutic relevance. However, their anticancer potential remains largely underinvestigated. Objectives: This study aimed to compare the phytochemical composition of hydroethanolic extracts from fresh (HEEF) and stored (HEES) saffron corms and to evaluate their anticancer effectiveness against colorectal cancer cells. Methods: Phytochemical profiling was performed using HPLC-ESI-QTOF-MS/MS. Cytotoxicity against T84 and SW480 colorectal cancer cell lines was determined by the crystal violet assay. Apoptosis-related protein modulation was assessed by Western blotting. Additionally, molecular docking, molecular dynamics simulations, and MM/GBSA calculations were used to investigate ligand–target binding affinities and stability. Results: Both extracts contained diverse primary and secondary metabolites, including phenolic acids, flavonoids, triterpenoids, lignans, anthraquinones, carotenoids, sugars, and fatty acids. HEES showed higher relative abundance of key bioactive metabolites than HEEF, which was enriched mainly in primary metabolites. HEES showed significantly greater dose-dependent cytotoxicity, particularly against SW480 cells after 24 h (IC50 = 34.85 ± 3.35). Apoptosis induction was confirmed through increased expression of caspase-9 and p53 in T84 cells. In silico studies revealed strong and stable interactions of major metabolites, especially 3,8-dihydroxy-1-methylanthraquinone-2-carboxylic acid with COX2 and crocetin with VEGFR2. Conclusions: Stored saffron corms possess a richer bioactive profile and show enhanced anticancer effects in vitro compared with fresh saffron corms, suggesting that they may represent a promising source of compounds for the future development of colorectal cancer therapeutics. 2026-02-05T11:17:35Z 2026-02-05T11:17:35Z 2026-01-14 journal article Baddaoui, S.; Saalaoui, E.; Khibech, O.; Salagre, D.; Fernández-Ochoa, Á.; Mamri, S.; Aktary, N.; Rahman, M.; Rani, A.; Asehraou, A.; et al. HPLC-ESI-QTOF-MS/MS-Guided Profiling of Bioactive Compounds in Fresh and Stored Saffron Corms Reveals Potent Anticancer Activity Against Colorectal Cancer. Pharmaceuticals 2026, 19, 149. [https://doi.org/10.3390/ph19010149] https://hdl.handle.net/10481/110681 10.3390/ph19010149 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional MDPI