关键词: Anticancer peptides Antimicrobial peptides Cap18 Cathelicidin

Mesh : Humans Animals Cell Line, Tumor Breast Neoplasms / drug therapy metabolism pathology Apoptosis / drug effects Cathelicidins Cyclin-Dependent Kinase 4 / metabolism genetics Female Rabbits Cell Movement / drug effects Antineoplastic Agents / pharmacology chemistry Antimicrobial Cationic Peptides / pharmacology Cyclin-Dependent Kinase 6 / metabolism Cell Cycle / drug effects Cell Proliferation / drug effects Peptides / pharmacology chemistry Gene Expression Regulation, Neoplastic / drug effects

来  源:   DOI:10.1038/s41598-024-64400-1   PDF(Pubmed)

Abstract:
Antimicrobial peptides (AMPs) have sparked significant interest as potential anti-cancer agents, thereby becoming a focal point in pursuing novel cancer-fighting strategies. These peptides possess distinctive properties, underscoring the importance of developing more potent and selectively targeted versions with diverse mechanisms of action against human cancer cells. Such advancements would offer notable advantages compared to existing cancer therapies. This research aimed to examine the toxicity and selectivity of the nrCap18 peptide in both cancer and normal cell lines. Furthermore, the rate of cellular death was assessed using apoptosis and acridine orange/ethidium bromide (AO/EB) double staining at three distinct incubation times. Additionally, the impact of this peptide on the cancer cell cycle and migration was evaluated, and ultimately, the expression of cyclin-dependent kinase 4/6 (CDK4/6) genes was investigated. The results obtained from the study demonstrated significant toxicity and selectivity in cancer cells compared to normal cells. Moreover, a strong progressive increase in cell death was observed over time. Furthermore, the peptide exhibited the ability to halt the progression of cancer cells in the G1 phase of the cell cycle and impede their migration by suppressing the expression of CDK4/6 genes.
摘要:
抗菌肽(AMP)作为潜在的抗癌剂引起了人们的极大兴趣,从而成为追求新型抗癌策略的焦点。这些肽具有独特的特性,强调开发具有针对人类癌细胞的多种作用机制的更有效和选择性靶向的版本的重要性。与现有的癌症疗法相比,这样的进步将提供显著的优势。这项研究旨在检查nrCap18肽在癌症和正常细胞系中的毒性和选择性。此外,在三个不同的孵育时间使用细胞凋亡和吖啶橙/溴化乙锭(AO/EB)双重染色评估细胞死亡速率.此外,评估了该肽对癌细胞周期和迁移的影响,最终,研究了细胞周期蛋白依赖性激酶4/6(CDK4/6)基因的表达。从研究中获得的结果表明,与正常细胞相比,癌细胞具有显着的毒性和选择性。此外,随着时间的推移,观察到细胞死亡的强烈进行性增加.此外,肽表现出阻止细胞周期G1期癌细胞进展的能力,并通过抑制CDK4/6基因的表达来阻止其迁移。
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