Peptide-based drugs have emerged as highly selective and potent cancer therapy. Cancer is one of the leading causes of death worldwide. Multiple approaches have been developed towards cancer treatment, including chemotherapy, radiation, and hormonal therapy; however, such procedures' non-specificity, toxicity, and inefficiency present a hurdle. In this study, we developed a support vector machine (SVM) model to detect the potential anticancer properties of novel peptides through scanning the American University in Cairo Red Sea metagenomics library. Further, we performed in silico studies on a novel 37-mer antimicrobial peptide mined from SVM pipeline analysis. This peptide was further modified to enhance its anticancer activity, analyzed for gene oncology, and subsequently synthesized. The anticancer properties of this 37-mer peptide were evaluated via cellular viability and cell morphology of SNU449, HepG2, SKOV3, and HeLa cells, using MTT assay. Furthermore, we assessed the migration capability of SNU449 and SKOV3 via scratch wound healing assay. Moreover, the targeted selectivity of the peptide for cancerous cells was assessed by testing its hemolytic activity on human erythrocytes. The peptide caused a significant reduction in cellular viability and critically affected the morphology of hepatocellular carcinoma (SNU449 and HepG2), ovarian cancer (SKOV3), and to a limited extent, cervical cancer cell lines (HeLa), in addition to decreasing viability of human fibroblast cell line (1Br-hTERT). Peptide treatment significantly affected the proliferation and migration ability of SNU449 and SKOV3 cells. Annexin V assay was used to evaluate induced cell death upon peptide treatment, attributing programmed cell death (Apoptosis) as the main cause of cell death in SNU449 cells. Finally, we established broad-spectrum antimicrobial properties of the peptide on both gram-positive and gram-negative bacterial strains. Thus, these findings infer the novelty of the peptide as a potential anticancer and antimicrobial agent.

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.