Development of a Novel Peptide with RGD Tumor Homing Motif: Evaluation of its Anticancer Potential in Hepatocellular Carcinoma and Colon Cancer Cells

Q3 Biochemistry, Genetics and Molecular Biology
Reda Abdallah Mohamed, Ohoud M. Marie, Dahlia I. Badran, O. Hammam, Hend Okasha
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引用次数: 0

Abstract

Peptide-based therapy has emerged as a promising avenue for treating various disorders, and recent research has highlighted the potential of anti-cancer peptides (ACPs) in cancer treatment. In this context, this study aimed to design a novel peptide incorporating a tumor-homing peptide (RGD) and C-amidation to enhance its anticancer activity, particularly against liver (HepG2) and colon (HCT-116) cancer cell lines. The primary objective was to design a peptide with improved anticancer properties by leveraging the tumor-homing capabilities of RGD and enhancing its activity through C-amidation. The study sought to evaluate the cytotoxicity of the designed peptide against red blood cells (RBCs) and normal Vero cells. Furthermore, the anticancer efficacy of the peptide was assessed in hepatocellular carcinoma (HepG2) and colon cancer (HCT-116) cell lines. The specific objectives included examining the apoptotic induction and morphological changes in treated cells compared to untreated cells. The peptide was designed using the ACPred-FL bioinformatics tool, and its cytotoxicity was assessed through hemolysis assays against RBCs and normal Vero cells. Anticancer activity was evaluated against HepG2 and HCT-116 cell lines. The analysis of apoptotic induction involved measuring the relative gene expression of oncogenic marker BCL2 and apoptotic markers (BAX, BID, CAS-8). Additionally, Cytopathological examination and Western Blot analysis were employed to study morphological changes and confirm the quantification of relevant markers. The designed peptide, consisting of twelve amino acids with a molecular mass of 1230.6233 Da and an isoelectric point of 9.81, exhibited low erythrocyte lysis and minimal toxicity to normal cells. The IC50 values demonstrated significant anticancer activity against both HepG2 (36.49±2.6 μg/mL) and HCT-116 (11.03±2.5 μg/mL) cell lines. Treated cells exhibited a significant decrease in the oncogenic marker BCL2 and an upregulation of apoptotic markers (BAX, BID, CAS-8). Western Blot analysis confirmed these findings, and Cytopathological examination revealed scattered apoptotic and degenerative changes. The designed peptide displayed remarkable anticancer activity against hepatocellular carcinoma and colon cancer cell lines, effectively modulating apoptotic and oncogenic markers. These findings highlight the potential of the peptide as a therapeutic agent for cancer treatment, emphasizing its clinical significance in combating liver and colon cancers. Nonetheless, further research and development are warranted to explore the translational potential of this peptide in clinical settings.
开发具有 RGD 肿瘤归巢基团的新型多肽:评估其在肝细胞癌和结肠癌细胞中的抗癌潜力
基于肽的疗法已成为治疗各种疾病的一种前景广阔的途径,最近的研究强调了抗癌肽(ACPs)在癌症治疗中的潜力。在此背景下,本研究旨在设计一种新型多肽,该多肽结合了肿瘤定位肽(RGD)和C-酰胺化,以增强其抗癌活性,尤其是针对肝癌(HepG2)和结肠癌(HCT-116)细胞系的抗癌活性。研究试图评估所设计的多肽对红细胞(RBC)和正常 Vero 细胞的细胞毒性。此外,还评估了该肽在肝癌(HepG2)和结肠癌(HCT-116)细胞系中的抗癌功效。该多肽是利用 ACPred-FL 生物信息学工具设计的,其毒性通过针对红细胞和正常 Vero 细胞的溶血试验进行评估。凋亡诱导分析包括测量致癌标记物 BCL2 和凋亡标记物(BAX、BID、CAS-8)的相对基因表达。所设计的肽由 12 个氨基酸组成,分子质量为 1230.6233 Da,等电点为 9.81,红细胞裂解率低,对正常细胞的毒性极小。其 IC50 值显示了对 HepG2(36.49±2.6 μg/mL)和 HCT-116 (11.03±2.5 μg/mL)细胞系的显著抗癌活性。经处理的细胞表现出致癌标记物 BCL2 的显著下降和凋亡标记物(BAX、BID、CAS-8)的上调。所设计的多肽对肝细胞癌和结肠癌细胞系具有显著的抗癌活性,能有效调节细胞凋亡和致癌标志物。这些发现凸显了多肽作为癌症治疗剂的潜力,强调了它在抗击肝癌和结肠癌方面的临床意义。尽管如此,仍需进一步研究和开发,以挖掘该肽在临床中的转化潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Recent patents on biotechnology
Recent patents on biotechnology Biochemistry, Genetics and Molecular Biology-Biotechnology
CiteScore
2.90
自引率
0.00%
发文量
51
期刊介绍: Recent Patents on Biotechnology publishes review articles by experts on recent patents on biotechnology. A selection of important and recent patents on biotechnology is also included in the journal. The journal is essential reading for all researchers involved in all fields of biotechnology.
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