Impact of camel milk lactoferrin peptides against breast cancer cells: in silico and in vitro study

Othman Baothman; Ehab M M Ali; Hassan Alguridi; Salman Hosawi; Emadeldin Hassan E Konozy; Isam M Abu Zeid; Abrar Ahmad; Hisham N Altayb

doi:10.3389/fphar.2024.1425504

Impact of camel milk lactoferrin peptides against breast cancer cells: in silico and in vitro study

Front Pharmacol. 2024 Nov 19:15:1425504. doi: 10.3389/fphar.2024.1425504. eCollection 2024.

Authors

Othman Baothman^{1

2}, Ehab M M Ali^{1

3}, Hassan Alguridi¹, Salman Hosawi^{1

2}, Emadeldin Hassan E Konozy^{4

5}, Isam M Abu Zeid⁶, Abrar Ahmad¹, Hisham N Altayb^{1

2}

Affiliations

¹ Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
² Center of Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah, Saudi Arabia.
³ Division of Biochemistry, Chemistry Department, Faculty of Science Tanta University, Tanta, Egypt.
⁴ Laboratory of Proteomics and Glycobiology, Biotechnology Department, Africa City of Technology, Khartoum, Sudan.
⁵ Biomedical and Clinical Research Centre (BCRC), College of Health and Allied Sciences (CoHAS), University of Cape Coast, Cape Coast, Ghana.
⁶ Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

Abstract

Background and aims: Breast cancer remains a significant global health concern, necessitating the exploration of novel therapeutic strategies. Despite advancements in cancer therapeutics, effective treatments with minimal side effects remain elusive. Natural sources, such as camel milk, harbor bioactive compounds such as lactoferrin peptides, which hold promise as anticancer agents. This study investigated the potential of camel milk-derived lactoferrin peptides against breast cancer cells through a combined in silico and in vitro approach. By integrating computational modeling with experimental assays, we aimed to elucidate the anticancer mechanisms of these peptides and provide insights for their optimization as anticancer therapeutics.

Methods: In silico analysis involving pepetid design, and validation, then molecular docking and molecular dynamics (MD) simulations was used to explore peptide-protein interactions and stability. Peptides were synthesized and tested for anticancer activity using MTT assays on MCF-7 cells, with HDFa normal cells used as controls.

Results: Results of this study showed that camel milk-derived lactoferrin peptides, particularly PEP66, exhibited strong anticancer activity against MCF-7 breast cancer cells, with the lowest IC50 value (52.82 μg/mL) compared to other peptides. In silico molecular docking and dynamics simulations revealed that PEP66 formed stable interactions with key residues in the HER2 catalytic site, indicating its potential as an effective anticancer agent. The selectivity index (SI) of PEP66 (3.19) also suggested lower toxicity to normal cells compared to cancer cells, reinforcing its therapeutic potential. Hydrogen bonding analysis highlighted key residues involved in stabilizing peptide-protein complexes, while molecular dynamics simulations demonstrated the stability of these interactions over time. Notably, PEP66 exhibited the highest stability and formed significant interactions with essential residues in the HER2 catalytic site, suggesting its potential as an effective anticancer agent.

Conclusion: Camel milk-derived lactoferrin peptides show promise as anticancer agents against breast cancer cells. The multidisciplinary approach employed in this study provides valuable insights into the mechanisms underlying their activity, paving the way for rational design strategies to enhance their efficacy. Further experimental validation is warranted to validate the anticancer potential of these peptides and advance their development as novel therapeutic agents for breast cancer treatment.

Keywords: HDFa normal cells; HER2 protein; MCF-7 breast cancer cells; camel milk; in silico.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The authors extend their appreciation to the Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia, for funding this research through project number IFPRC-165-130-2020 and King Abdulaziz University DSR, Jeddah, Saudi Arabia.