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

peer-reviewed · Scientific Reports · 2025

peer-reviewed · Scientific Reports · 2025. Ahmed A. A. Hussein et al. Bioactive peptides have recently emerged as promising candidates for cancer treatment due to their selective…
Date 2025-10-01
Type peer-reviewed
Venue Scientific Reports
Publisher Springer Science and Business Media LLC
Contribution downstream-application
DOI 10.1038/s41598-025-20094-7
Citations (OpenAlex) 3
Venue 2-year citedness 5.08

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.

Authors

  1. Ahmed A. A. Hussein · Theodor Bilharz Research Institute
  2. Maha B. Salem · Theodor Bilharz Research Institute
  3. Mohamed ElZallat · Theodor Bilharz Research Institute
  4. Samah I. Ghoname · Theodor Bilharz Research Institute
  5. Mohamed R. Habib · Theodor Bilharz Research Institute
  6. Olfat Ali Hammam · Theodor Bilharz Research Institute
  7. Ehab El-Dabaa · Theodor Bilharz Research Institute
  8. Hend Okasha · Theodor Bilharz Research Institute

Methods and tools

  • Ruditapes decussatus anticancer peptides: De novo sequencing of 135 peptides purified from the edible clam Ruditapes decussatus, 57 of them predicted to have anticancer activity, with fractions cytotoxic to liver and colorectal cancer cell lines.

Data deposited

  • Novel peptides from the edible bivalve Ruditapes decussatus target apoptosis, autophagy, and FGF19-FGFR4 signaling in human cancer cell lines — as deposited · PXD067801

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