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

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Hussein A.A.A.; Salem M.B.; ElZallat M.; Ghoname S.I.; Habib M.R.; Hammam O.A.; El-Dabaa E.; Okasha H.

Journal: Scientific Reports

Publisher: Nature Research

Publication Date: 1 October 2025

Volume / Issue: Volume 15 / Issue 1

Article No.: 34283

ISSN: 20452322

DOI: 10.1038/s41598-025-20094-7

Scopus: View on Scopus

PubMed: 41034324

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Hussein A.A.A., Department of Medical Malacology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; Salem M.B., Department of Pharmacology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; ElZallat M., Department of Immunology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; Ghoname S.I., Department of Medical Malacology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; Habib M.R., Department of Medical Malacology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; Hammam O.A., Department of Pathology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; El-Dabaa E., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; Okasha H., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt

Abstract

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. © The Author(s) 2025.

Keywords

Anticancer activity; Bioactive peptides; Bivalves; Mass spectrometry; Natural agents; Animals; Antineoplastic Agents; Apoptosis; Autophagy; Bivalvia; Cell Line, Tumor; Chlorocebus aethiops; Fibroblast Growth Factors; Hep G2 Cells; HT29 Cells; Humans; Peptides; Signal Transduction; Vero Cells; antineoplastic agent; fibroblast growth factor; peptide; animal; bivalve; chemistry; drug effect; Hep-G2 cell line; HT-29 cell line; human; isolation and purification; metabolism; tumor cell line; Vero cell line

Citation Information

Scopus Citations: 2

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