Hashem Sheema, Bhat Ajaz A, Nisar Sabah, Uddin Shahab, Merhi Maysaloun, Mateo Jericha M, Prabhu Kirti S, Soubra Lama, Dos Santos Silva Carlos André, Benko-Iseppon Ana Maria, Vilela Lívia Maria Batista, de Lima Marx Oliveira, da Silva Juliana Georgia, Haris Mohammad, Suleman Muhammad, Crovella Sergio, Abou Saleh Haissam
Environmental Science Program, Department of Biological and Environmental Sciences, College of Arts and Science, Qatar University, Doha, Qatar.
Department of Human Genetics, Sidra Medicine, Doha, Qatar.
Curr Protein Pept Sci. 2025 Feb 11. doi: 10.2174/0113892037363898250110053529.
Colorectal cancer (CRC) is one of the most common malignancies worldwide, and despite advances in treatment, there remains a critical need for novel therapeutic approaches. Recently, anti-microbial peptides (AMPs) have gained attention for their potential use in cancer therapy due to their selective cytotoxicity towards cancer cells.
This study aims to evaluate the anti-cancer potential of two computationally engineered anti-microbial peptides (EAMPs) in SW620, SW480, and HCT116 colon cancer cells and the normal colon epithelial cell line CCD 841, focusing on their effects on cell proliferation, apoptosis, and DNA damage.
Cell proliferation and survival were measured using the CellTiter-Glo Luminescence and clonogenic assays. DNA damage was assessed through the Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Flow cytometry was used to examine cell apoptosis, cell cycle distribution, and mitochondrial membrane potential in SW620 cells.
EAMPs inhibited CRC cell proliferation in a dose-dependent manner, with minimal toxicity observed in normal colon epithelial cells. In SW620 cells, EAMPs induced DNA damage, resulting in cell cycle arrest at the S/G2 phase, apoptosis, and a reduction in mitochondrial membrane potential. The proliferation results were confirmed in SW480 and HCT116 CRC cell lines.
Our findings revealed that EAMPs exhibited significant anti-cancer activity against CRC cells in vitro while sparing normal epithelial cells. These results suggest that EAMPs may offer a potential therapeutic approach for colorectal cancer and warrant further investigation.
结直肠癌（CRC）是全球最常见的恶性肿瘤之一，尽管治疗取得了进展，但对新型治疗方法仍有迫切需求。最近，抗菌肽（AMPs）因其对癌细胞的选择性细胞毒性而在癌症治疗中的潜在应用受到关注。
本研究旨在评估两种通过计算机设计的抗菌肽（EAMPs）对SW620、SW480和HCT116结肠癌细胞以及正常结肠上皮细胞系CCD 841的抗癌潜力，重点关注它们对细胞增殖、凋亡和DNA损伤的影响。
使用CellTiter-Glo发光法和克隆形成试验测量细胞增殖和存活。通过末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）试验评估DNA损伤。采用流式细胞术检测SW620细胞的凋亡、细胞周期分布和线粒体膜电位。
EAMPs以剂量依赖性方式抑制CRC细胞增殖，在正常结肠上皮细胞中观察到的毒性最小。在SW620细胞中，EAMPs诱导DNA损伤，导致细胞周期停滞在S/G2期，引发凋亡，并降低线粒体膜电位。在SW480和HCT116 CRC细胞系中证实了增殖结果。
我们的研究结果表明，EAMPs在体外对CRC细胞表现出显著的抗癌活性，同时对正常上皮细胞无损害。这些结果表明，EAMPs可能为结直肠癌提供一种潜在的治疗方法，值得进一步研究。
