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Anticancer Activity of the Goat Antimicrobial Peptide ChMAP-28.

ABSTRACT: Cytotoxic effect of the antimicrobial peptide ChMAP-28 from leucocytes of the goat Capra hircus was examined against five cancer and two normal human cell lines. ChMAP-28 has the amino acid sequence GRFKRFRKKLKRLWHKVGPFVGPILHY and is homologous to other ?-helical mammalian antimicrobial peptides. ChMAP-28 shows considerably higher cytotoxicity against cultured tumor cells than toward normal cells at concentrations of <10 ?M. Our findings suggest that ChMAP-28 can initiate necrotic death of cancer cells. Its cytotoxic effect is accomplished due to disruption of the plasma membrane integrity and is not abrogated by the addition of the caspase inhibitor Z-VAD-FMK. ChMAP-28 causes permeabilization of cytoplasmic membrane of human leukemia cells HL-60 already after 15 min of incubation. Here, we show that ChMAP-28 has one of the highest antitumor activity in vitro among all known antimicrobial peptides. We speculate that the observed specificity of ChMAP-28 cytotoxic effect against tumor cells is due to its relatively low hydrophobicity and high cationicity. In the meantime, this peptide has low hemolytic activity, which generates a potential for its use as a therapeutic agent.

SUBMITTER: Emelianova AA

PROVIDER: S-EPMC6308165 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Anticancer Activity of the Goat Antimicrobial Peptide ChMAP-28.

Emelianova Anna A AA Kuzmin Denis V DV Panteleev Pavel V PV Sorokin Maxim M Buzdin Anton A AA Ovchinnikova Tatiana V TV

Frontiers in pharmacology 20181221

Cytotoxic effect of the antimicrobial peptide ChMAP-28 from leucocytes of the goat <i>Capra hircus</i> was examined against five cancer and two normal human cell lines. ChMAP-28 has the amino acid sequence GRFKRFRKKLKRLWHKVGPFVGPILHY and is homologous to other α-helical mammalian antimicrobial peptides. ChMAP-28 shows considerably higher cytotoxicity against cultured tumor cells than toward normal cells at concentrations of <10 μM. Our findings suggest that ChMAP-28 can initiate necrotic death o ...[more]

PMID: 30622471

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Project description:Cancer associated drug resistance is a major cause for cancer aggravation, particularly as conventional therapies have presented limited efficiency, low specificity, resulting in long term deleterious side effects. Peptide based drugs have emerged as potential alternative cancer treatment tools due to their selectivity, ease of design and synthesis, safety profile, and low cost of manufacturing. In this study, we utilized the Red Sea metagenomics database, generated during AUC/KAUST Red Sea microbiome project, to derive a viable anticancer peptide (ACP). We generated a set of peptide hits from our library that shared similar composition to ACPs. A peptide with a homeodomain was selected, modified to improve its anticancer properties, verified to maintain high anticancer properties, and processed for further in-silico prediction of structure and function. The peptide's anticancer properties were then assessed in vitro on osteosarcoma U2OS cells, through cytotoxicity assay (MTT assay), scratch-wound healing assay, apoptosis/necrosis detection assay (Annexin/PI assay), RNA expression analysis of Caspase 3, KI67 and Survivin, and protein expression of PARP1. L929 mouse fibroblasts were also assessed for cytotoxicity treatment. In addition, the antimicrobial activity of the peptide was also examined on E coli and S. aureus, as sample representative species of the human bacterial microbiome, by examining viability, disk diffusion, morphological assessment, and hemolytic analysis. We observed a dose dependent cytotoxic response from peptide treatment of U2OS, with a higher tolerance in L929s. Wound closure was debilitated in cells exposed to the peptide, while annexin fluorescent imaging suggested peptide treatment caused apoptosis as a major mode of cell death. Caspase 3 gene expression was not altered, while KI67 and Survivin were both downregulated in peptide treated cells. Additionally, PARP-1 protein analysis showed a decrease in expression with peptide exposure. The peptide exhibited minimal antimicrobial activity on critical human microbiome species E. coli and S. aureus, with a low inhibition rate, maintenance of structural morphology and minimal hemolytic impact. These findings suggest our novel peptide displayed preliminary ACP properties against U2OS cells, through limited specificity, while triggering apoptosis as a primary mode of cell death and while having minimal impact on the microbiological species E. coli and S. aureus.

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Anticancer Activity of the Goat Antimicrobial Peptide ChMAP-28.

Publications

Anticancer Activity of the Goat Antimicrobial Peptide ChMAP-28.

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