Baothman Othman, Ali Ehab M M, Alguridi Hassan, Hosawi Salman, Konozy Emadeldin Hassan E, Abu Zeid Isam M, Ahmad Abrar, Altayb Hisham N
Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Center of Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah, Saudi Arabia.
Front Pharmacol. 2024 Nov 19;15:1425504. doi: 10.3389/fphar.2024.1425504. eCollection 2024.
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 and 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.
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 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. 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.
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.
乳腺癌仍然是一个重大的全球健康问题，因此有必要探索新的治疗策略。尽管癌症治疗取得了进展，但副作用最小的有效治疗方法仍然难以实现。天然来源，如骆驼奶，含有生物活性化合物，如乳铁蛋白肽，有望成为抗癌剂。本研究通过结合计算建模和实验分析的方法，研究了骆驼奶来源的乳铁蛋白肽对乳腺癌细胞的潜在作用。通过将计算建模与实验分析相结合，我们旨在阐明这些肽的抗癌机制，并为其作为抗癌治疗药物的优化提供见解。
采用涉及肽设计、验证，然后进行分子对接和分子动力学（MD）模拟的分析方法，以探索肽-蛋白质相互作用和稳定性。合成肽并使用MTT法在MCF-7细胞上测试其抗癌活性，以HDFa正常细胞作为对照。
本研究结果表明，骆驼奶来源的乳铁蛋白肽，特别是PEP66，对MCF-7乳腺癌细胞表现出强大的抗癌活性，与其他肽相比，其IC50值最低（52.82μg/mL）。分子对接和动力学模拟表明，PEP66与HER2催化位点的关键残基形成稳定的相互作用，表明其作为有效抗癌剂的潜力。PEP66的选择性指数（SI）（3.19）也表明与癌细胞相比，其对正常细胞的毒性较低，增强了其治疗潜力。氢键分析突出了参与稳定肽-蛋白质复合物的关键残基，而分子动力学模拟证明了这些相互作用随时间的稳定性。值得注意的是，PEP66表现出最高的稳定性，并与HER2催化位点的必需残基形成显著相互作用，表明其作为有效抗癌剂的潜力。
骆驼奶来源的乳铁蛋白肽有望成为抗乳腺癌细胞的抗癌剂。本研究采用的多学科方法为其活性背后的机制提供了有价值的见解，为合理设计策略以提高其疗效铺平了道路。需要进一步的实验验证来证实这些肽的抗癌潜力，并推动其作为乳腺癌治疗新治疗剂的开发。
