Exploiting Zebrafish Xenografts for Testing the in vivo Antitumorigenic Activity of Microcin E492 Against Human Colorectal Cancer Cells
One of the approaches to address cancer treatment is to develop new drugs not only to obtain compounds with less side effects, but also to have a broader set of alternatives to tackle the resistant forms of this pathology. In this regard, growing evidence supports the use of bacteria-derived peptide...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2020.00405/full |
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| author | Macarena A. Varas Carlos Muñoz-Montecinos Violeta Kallens Valeska Simon Miguel L. Allende Andrés E. Marcoleta Rosalba Lagos |
| author_facet | Macarena A. Varas Carlos Muñoz-Montecinos Violeta Kallens Valeska Simon Miguel L. Allende Andrés E. Marcoleta Rosalba Lagos |
| author_sort | Macarena A. Varas |
| collection | DOAJ |
| description | One of the approaches to address cancer treatment is to develop new drugs not only to obtain compounds with less side effects, but also to have a broader set of alternatives to tackle the resistant forms of this pathology. In this regard, growing evidence supports the use of bacteria-derived peptides such as bacteriocins, which have emerged as promising anti-cancer molecules. In addition to test the activity of these molecules on cancer cells in culture, their in vivo antitumorigenic properties must be validated in animal models. Although the standard approach for such assays employs experiments in nude mice, at the initial stages of testing, the use of high-throughput animal models would permit rapid proof-of-concept experiments, screening a high number of compounds, and thus increasing the possibilities of finding new anti-cancer molecules. A validated and promising alternative animal model are zebrafish larvae harboring xenografts of human cancer cells. Here, we addressed the anti-cancer properties of the antibacterial peptide microcin E492 (MccE492), a bacteriocin produced by Klebsiella pneumoniae, showing that this peptide has a marked cytotoxic effect on human colorectal cancer cells in vitro. Furthermore, we developed a zebrafish xenograft model using these cells to test the antitumor effect of MccE492 in vivo, demonstrating that intratumor injection of this peptide significantly reduced the tumor cell mass. Our results provide, for the first time, evidence of the in vivo antitumoral properties of a bacteriocin tested in an animal model. This evidence strongly supports the potential of this bacteriocin for the development of novel anti-cancer therapies. |
| first_indexed | 2024-12-13T10:28:45Z |
| format | Article |
| id | doaj.art-08970fe2264749f8afcf1e981a3ce71c |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-13T10:28:45Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-08970fe2264749f8afcf1e981a3ce71c2022-12-21T23:50:56ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-03-011110.3389/fmicb.2020.00405492896Exploiting Zebrafish Xenografts for Testing the in vivo Antitumorigenic Activity of Microcin E492 Against Human Colorectal Cancer CellsMacarena A. Varas0Carlos Muñoz-Montecinos1Violeta Kallens2Valeska Simon3Miguel L. Allende4Andrés E. Marcoleta5Rosalba Lagos6Laboratorio de Biología Estructural y Molecular BEM, Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago, ChileDepartamento de Biología, Facultad de Ciencias, FONDAP Center for Genome Regulation, Universidad de Chile, Santiago, ChileDepartamento de Biología, Facultad de Ciencias, FONDAP Center for Genome Regulation, Universidad de Chile, Santiago, ChileLaboratorio de Inmunología, Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago, ChileDepartamento de Biología, Facultad de Ciencias, FONDAP Center for Genome Regulation, Universidad de Chile, Santiago, ChileLaboratorio de Biología Estructural y Molecular BEM, Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago, ChileLaboratorio de Biología Estructural y Molecular BEM, Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago, ChileOne of the approaches to address cancer treatment is to develop new drugs not only to obtain compounds with less side effects, but also to have a broader set of alternatives to tackle the resistant forms of this pathology. In this regard, growing evidence supports the use of bacteria-derived peptides such as bacteriocins, which have emerged as promising anti-cancer molecules. In addition to test the activity of these molecules on cancer cells in culture, their in vivo antitumorigenic properties must be validated in animal models. Although the standard approach for such assays employs experiments in nude mice, at the initial stages of testing, the use of high-throughput animal models would permit rapid proof-of-concept experiments, screening a high number of compounds, and thus increasing the possibilities of finding new anti-cancer molecules. A validated and promising alternative animal model are zebrafish larvae harboring xenografts of human cancer cells. Here, we addressed the anti-cancer properties of the antibacterial peptide microcin E492 (MccE492), a bacteriocin produced by Klebsiella pneumoniae, showing that this peptide has a marked cytotoxic effect on human colorectal cancer cells in vitro. Furthermore, we developed a zebrafish xenograft model using these cells to test the antitumor effect of MccE492 in vivo, demonstrating that intratumor injection of this peptide significantly reduced the tumor cell mass. Our results provide, for the first time, evidence of the in vivo antitumoral properties of a bacteriocin tested in an animal model. This evidence strongly supports the potential of this bacteriocin for the development of novel anti-cancer therapies.https://www.frontiersin.org/article/10.3389/fmicb.2020.00405/fullmicrocin E492antitumorigenic peptidezebrafish xenograftbacteriocincolorectal cancerhuman cell lines |
| spellingShingle | Macarena A. Varas Carlos Muñoz-Montecinos Violeta Kallens Valeska Simon Miguel L. Allende Andrés E. Marcoleta Rosalba Lagos Exploiting Zebrafish Xenografts for Testing the in vivo Antitumorigenic Activity of Microcin E492 Against Human Colorectal Cancer Cells Frontiers in Microbiology microcin E492 antitumorigenic peptide zebrafish xenograft bacteriocin colorectal cancer human cell lines |
| title | Exploiting Zebrafish Xenografts for Testing the in vivo Antitumorigenic Activity of Microcin E492 Against Human Colorectal Cancer Cells |
| title_full | Exploiting Zebrafish Xenografts for Testing the in vivo Antitumorigenic Activity of Microcin E492 Against Human Colorectal Cancer Cells |
| title_fullStr | Exploiting Zebrafish Xenografts for Testing the in vivo Antitumorigenic Activity of Microcin E492 Against Human Colorectal Cancer Cells |
| title_full_unstemmed | Exploiting Zebrafish Xenografts for Testing the in vivo Antitumorigenic Activity of Microcin E492 Against Human Colorectal Cancer Cells |
| title_short | Exploiting Zebrafish Xenografts for Testing the in vivo Antitumorigenic Activity of Microcin E492 Against Human Colorectal Cancer Cells |
| title_sort | exploiting zebrafish xenografts for testing the in vivo antitumorigenic activity of microcin e492 against human colorectal cancer cells |
| topic | microcin E492 antitumorigenic peptide zebrafish xenograft bacteriocin colorectal cancer human cell lines |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2020.00405/full |
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