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从红海盐水池中提取的新型肽的特性分析及其抗癌活性的改良。

Characterization of a novel peptide mined from the Red Sea brine pools and modified to enhance its anticancer activity.

机构信息

Biotechnology Program, American University in Cairo, New Cairo, Egypt.

Biology Department, American University in Cairo, New Cairo, Egypt.

出版信息

BMC Cancer. 2023 Jul 26;23(1):699. doi: 10.1186/s12885-023-11045-4.

Abstract

Drug resistance is a major cause of the inefficacy of conventional cancer therapies, and often accompanied by severe side effects. Thus, there is an urgent need to develop novel drugs with low cytotoxicity, high selectivity and minimal acquired chemical resistance. Peptide-based drugs (less than 0.5 kDa) have emerged as a potential approach to address these issues due to their high specificity and potent anticancer activity. In this study, we developed a support vector machine model (SVM) to detect the potential anticancer properties of novel peptides by scanning the American University in Cairo (AUC) Red Sea metagenomics library. We identified a novel 37-mer antimicrobial peptide through SVM pipeline analysis and characterized its anticancer potential through in silico cross-examination. The peptide sequence was further modified to enhance its anticancer activity, analyzed for gene ontology, and subsequently synthesized. To evaluate the anticancer properties of the modified 37-mer peptide, we assessed its effect on the viability and morphology of SNU449, HepG2, SKOV3, and HeLa cells, using an MTT assay. Additionally, we evaluated the migration capabilities of SNU449 and SKOV3 cells using a scratch-wound healing assay. The targeted selectivity of the modified peptide was examined by evaluating its hemolytic activity on human erythrocytes. Treatment with the peptide significantly reduced cell viability and had a critical impact on the morphology of hepatocellular carcinoma (SNU449 and HepG2), and ovarian cancer (SKOV3) cells, with a marginal effect on cervical cancer cell lines (HeLa). The viability of a human fibroblast cell line (1Br-hTERT) was also significantly reduced by peptide treatment, as were the proliferation and migration abilities of SNU449 and SKOV3 cells. The annexin V assay revealed programmed cell death (apoptosis) as one of the potential cellular death pathways in SNU449 cells upon peptide treatment. Finally, the peptide exhibited antimicrobial effects on both gram-positive and gram-negative bacterial strains. The findings presented here suggest the potential of our novel peptide as a potent anticancer and antimicrobial agent.

摘要

耐药性是常规癌症疗法无效的主要原因,并且常伴有严重的副作用。因此,迫切需要开发具有低细胞毒性、高选择性和最小获得性化学耐药性的新型药物。由于其高特异性和强大的抗癌活性,基于肽的药物(小于 0.5 kDa)已成为解决这些问题的一种潜在方法。在这项研究中,我们通过扫描美国开罗大学(AUC)红海宏基因组文库,开发了一种支持向量机模型(SVM)来检测新型肽的潜在抗癌特性。我们通过 SVM 管道分析鉴定了一种新型的 37 肽抗菌肽,并通过计算机交叉检查来表征其抗癌潜力。进一步修饰肽序列以增强其抗癌活性,进行基因本体分析,并随后合成。为了评估修饰的 37 肽的抗癌特性,我们使用 MTT 测定法评估了其对 SNU449、HepG2、SKOV3 和 HeLa 细胞活力和形态的影响。此外,我们使用划痕愈合测定法评估了 SNU449 和 SKOV3 细胞的迁移能力。通过评估修饰肽对人红细胞的溶血活性来检查其靶向选择性。肽处理显著降低了细胞活力,并对肝癌(SNU449 和 HepG2)和卵巢癌(SKOV3)细胞的形态产生了重大影响,对宫颈癌细胞系(HeLa)的影响较小。肽处理还显著降低了人成纤维细胞系(1Br-hTERT)的活力,以及 SNU449 和 SKOV3 细胞的增殖和迁移能力。Annexin V 测定显示,在 SNU449 细胞中,程序性细胞死亡(细胞凋亡)是肽处理后的潜在细胞死亡途径之一。最后,该肽对革兰氏阳性和革兰氏阴性细菌菌株均具有抗菌作用。这里提出的研究结果表明,我们的新型肽作为一种有效的抗癌和抗菌剂具有潜在的应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/592b/10369728/350653f362d4/12885_2023_11045_Fig1_HTML.jpg

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