Marine-derived peptides from Rapana venosa inhibit breast cancer cell growth through synergistic mechanisms with doxorubicin

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Saleh M.A.; Masoud H.M.M.; Habib M.R.; AbdElGhany S.R.; Amer M.E.; Abouel-Nour M.F.

Journal: Scientific Reports

Publisher: Nature Research

Publication Date: 12 September 2025

Volume / Issue: Volume 15 / Issue 1

Article No.: 32451

ISSN: 20452322

DOI: 10.1038/s41598-025-18052-4

Scopus: View on Scopus

PubMed: 40940399

Document Type: Article

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

Authors and Affiliations

Saleh M.A., Zoology Department, Faculty of Science, Mansoura University, Dakahlia Governorate, Mansoura, Egypt; Masoud H.M.M., Molecular Biology Department, National Research Centre, 33 El-Buhouth St., Giza, Dokki, 12622, Egypt, Proteome Research Laboratory, Central Laboratories Network and Centers of Excellence, National Research Centre, 33 El-Buhouth St., Giza, Dokki, 12622, Egypt; Habib M.R., Medical Malacology Department, Theodor Bilharz Research Institute, 1 Corniche El Nile St., Warrak El-Haddar, Giza, Imbaba, 12411, Egypt; AbdElGhany S.R., Zoology Department, Faculty of Science, Mansoura University, Dakahlia Governorate, Mansoura, Egypt; Amer M.E., Zoology Department, Faculty of Science, Mansoura University, Dakahlia Governorate, Mansoura, Egypt; Abouel-Nour M.F., Zoology Department, Faculty of Science, Mansoura University, Dakahlia Governorate, Mansoura, Egypt

Abstract

Marine natural products are a promising source of novel anticancer agents. This study evaluated the antitumor activity of peptide fractions derived from the marine gastropod Rapana venosa against human breast cancer cell lines MCF-7 (estrogen receptor-positive) and MDA-MB-231 (triple-negative). Peptides were isolated by enzymatic hydrolysis and Fast Protein Liquid Chromatography. All seven isolated fractions were systematically screened against four human cancer cell lines (MCF-7, MDA-MB-231, CaCo-2, and HepG2) to assess cancer type selectivity. Cytotoxicity was assessed using MTT assay, while cell cycle progression and apoptosis were analyzed by flow cytometry. Gene expression changes were examined by RT-qPCR. Two peptide fractions, RV1 and RV2, demonstrated remarkable selectivity for breast cancer cells, exhibiting 25–95-fold higher potency compared to other cancer types. These fractions showed significant dose-dependent cytotoxicity with IC50 values of 6.887–7.288 μg/ml (RV1) and 4.886–6.268 μg/ml (RV2) against breast cancer cells. Both fractions induced G0/G1 cell cycle arrest and promoted apoptosis through multiple pathways, upregulating pro-apoptotic genes (TP53, AIFM1, CASP3, BAX) and downregulating anti-apoptotic markers (BCL2, miR-155). Most significantly, combination treatments with doxorubicin resulted in remarkable synergistic effects, with RV2 + doxorubicin achieving 78.9% total apoptosis compared to 33.5% with doxorubicin alone. These results indicate that R. venosa-derived peptides exert selective anticancer effects against breast cancer cells through multiple mechanisms. The observed selectivity and synergism with doxorubicin suggest their potential as targeted adjuvant agents in combination chemotherapy. Further structural characterization and in vivo studies are needed to advance their therapeutic development. © The Author(s) 2025.

Keywords

Apoptosis; Breast cancer; Cell cycle; Doxorubicin; Marine peptides; Rapana venosa; Animals; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Drug Synergism; Female; Gastropoda; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; Peptides; Snails; antineoplastic agent; peptide; animal; breast tumor; chemistry; drug effect; drug potentiation; drug therapy; gastropod; gene expression regulation; human; isolation and purification; MCF-7 cell line; metabolism; pathology; snail; tumor cell line

Citation Information

Scopus Citations: 7

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