Novel peptides from the edible bivalve Ruditapes decussatus target apoptosis, autophagy, and FGF19-FGFR4 signaling in human cancer cell lines.

Bioactive peptides have recently emerged as promising candidates for cancer treatment due to their selective cytotoxicity toward cancer cells. The bivalve mollusk Ruditapes decussatus contains bioactive compounds that have not been thoroughly investigated for their potential anticancer properties. In this study, isolation and purification of peptide mixtures from R. decussatus were performed using FPLC chromatography followed by de novo sequence analysis. Using de novo peptide sequencing, a total of 135 peptides (ranging from 2681.6 to 5925.12 Da) were identified, of which 57 peptides (42%) were predicted to exhibit anticancer potential upon analysis with AntiCP 2.0, highlighting their possible therapeutic utility (Data are available via ProteomeXchange with identifier PXD067801). Additionally, fractions were tested against liver (HepG2) and colorectal (HT-29) cancer cell lines, as well as normal human hepatocytes and VERO (obtained from kidney) cells, to evaluate their cytotoxic effects. Fractions 2 and 3 showed significant anticancer activity against both cancer cell lines, while exhibiting minimal cytotoxicity toward normal cells. These fractions induced apoptosis, as evidenced by the downregulation of Bcl-2 and upregulation of caspase-3, and also activated autophagy, marked by increased Beclin-1 expression. Flow cytometry analysis revealed enhanced apoptotic cell death and G1/S phase cell cycle arrest in the treated cancer cells. Morphological analysis further confirmed the presence of apoptotic changes. Overall, the peptides derived from R. decussatus demonstrated the ability to induce apoptosis and cell cycle arrest in cancer cells, with a highly selective effect on colorectal carcinoma, suggesting their potential as anticancer agents for further investigation.