Selenium-enriched peptides isolated from Cardamine violifolia are potent in suppressing proliferation and enhancing apoptosis of HepG2 cells.

Selenium (Se)-enriched peptides were isolated from Cardamine violifolia by enzymatic hydrolysis and ultrafiltration. S3 (molecular weight [MW] distribution of 3-5 kDa) exhibited the strongest inhibitory effect on HepG2 cells and was thus screened using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay; it was found to have a high organic Se content. Its amino acid sequence was determined using HPLC-MS/MS. We then examined its ability to inhibit tumor cell proliferation and found that it arrested tumor cells in the S phase; moreover, it could induce cancer cell apoptosis. Following S3 treatment, we observed a decrease in mitochondrial membrane potential and an increase in cell calcium content. Upon S3 treatment at 60 µg/ml, the relative activities of caspase-3 and caspase-9 increased by 1.48 times and 2.17 times, and the contents of PI3K and AKT decreased from 2.05 ng/L and 1.95 ng/L to 0.71 ng/L and 0.50 ng/L, respectively, when compared with the control group. Transcriptomic analysis revealed significant changes in the PI3K-AKT pathway following S3 treatment. This study thus established a foundation for additional development of Se-enriched peptides from C. violifolia as a functional food. PRACTICAL APPLICATION: Cardamine violifolia is a Se-tolerant cruciferous plant that can metabolically transform inorganic Se into organic Se that exists in the form of a selenoprotein. Se-enriched peptide obtained by extraction and enzymolysis of selenoprotein, as an organic combination of organic Se and peptide, possess valuable biological activities. In this paper, the effect of Se-enriched peptides of C. violifolia on tumor cells was studied via cell experiments, and its mechanism was preliminarily discussed, which should provide a theoretical basis for developing functional foods containing C. violifolia.