Bifunctional β-Conglycinins from legumes suppress aflatoxin formation and colon carcinogenesis.

Safe natural antifungal and anticancer agents are increasingly needed. This study investigated β-conglycinin glycoproteins from chickpea, soybean, and lupin seeds for their dual antifungal and anticancer potential. Proteins were isolated and tested against Aspergillus spp. (A. flavus, A. niger, A. parasiticus) and colon cancer cell lines (DLD-1, SW620, HCT8, HT29). MIC values, sporulation, aflatoxin inhibition, and cell wall integrity assays (β-1,3-glucan, chitin, SEM imaging, and leakage) reflected the antifungal activity of the studied proteins, while cell viability, apoptosis markers, migration assays, and biomarker expression evaluated their anticancer activity. Bioinformatic analyzed the structural and physicochemical properties. Lupin β-conglycinin showed the most decisive antifungal action, reducing growth, sporulation, and aflatoxin production while disrupting fungal walls. It selectively reduced the viability of colon cancer cells while sparing normal cells, induced apoptosis (via caspase-3 and -9 activation), inhibited migration, and downregulated tumor biomarkers (CEA, FOXQ1, VEGFA, CXCL16, CXCL17, LGR5, and LGR6). Structural modeling revealed a compact 3D conformation, a high ratio of hydrophilic to hydrophobic residues, and a unique N-linked glycosylation site. This study provides the first integrated evidence of β-conglycinin's dual role, particularly from lupin, as both a fungal toxin inhibitor and an anticancer agent, highlighting its potential as a safe natural therapeutic.