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Open AccessArticle

CLytA-DAAO, Free and Immobilized in Magnetic Nanoparticles, induces Cell Death in Human Cancer Cells

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Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL). C/Maestro Alonso, 10. 03005 Alicante, Spain
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Unidad de Investigación. Hospital General Universitario de Elche, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO). Camí de l’Almazara, 11. 03203 Elche (Alicante), Spain
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Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández. Avda. Universidad s/n, Ed. Torregaitán. 03202 Elche (Alicante), Spain
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Centro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas. C/ Ramiro de Maeztu, 9, 28040, Madrid, Spain
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Unidad de Genética Molecular. Hospital General Universitario de Elche. Camí de l’Almazara, 11., 03203 Elche (Alicante), Spain
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Author to whom correspondence should be addressed.
Biomolecules 2020, 10(2), 222; https://doi.org/10.3390/biom10020222
Received: 13 January 2020 / Revised: 30 January 2020 / Accepted: 31 January 2020 / Published: 3 February 2020
(This article belongs to the Special Issue Mechanisms of Cell Death in Disease: A New Therapeutic Opportunity)
D-amino acid oxidase (DAAO) catalyzes the oxidation of D-amino acids generating hydrogen peroxide, a potential producer of reactive oxygen species. In this study, we used a CLytA-DAAO chimera, both free and bound to magnetic nanoparticles, against colon carcinoma, pancreatic adenocarcinoma, and glioblastoma cell lines. We found that the enzyme induces cell death in most of the cell lines tested and its efficiency increases significantly when it is immobilized in nanoparticles. We also tested this enzyme therapy in non-tumor cells, and we found that there is not cell death induction, or it is significantly lower than in tumor cells. The mechanism triggering cell death is apparently a classical apoptosis pathway in the glioblastoma cell lines, while in colon and pancreatic carcinoma cell lines, CLytA-DAAO-induced cell death is a necrosis. Our results constitute a proof of concept that an enzymatic therapy, based on magnetic nanoparticles-delivering CLytA-DAAO, could constitute a useful therapy against cancer and besides it could be used as an enhancer of other treatments such as epigenetic therapy, radiotherapy, and treatments based on DNA repair.
Keywords: magnetic nanoparticle; cancer therapy; reactive oxygen species; oxidative damage; cytotoxicity; choline-binding proteins magnetic nanoparticle; cancer therapy; reactive oxygen species; oxidative damage; cytotoxicity; choline-binding proteins
MDPI and ACS Style

Fuentes-Baile, M.; Bello-Gil, D.; Pérez-Valenciano, E.; Sanz, J.M.; García-Morales, P.; Maestro, B.; Ventero, M.P.; Alenda, C.; Barberá, V.M.; Saceda, M. CLytA-DAAO, Free and Immobilized in Magnetic Nanoparticles, induces Cell Death in Human Cancer Cells. Biomolecules 2020, 10, 222.

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