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

Biomolecules

卷:10

Cristina Alenda¹  MaríaP. Ventero¹  María Fuentes-Baile¹  Beatriz Maestro²  Daniel Bello-Gil²  Elizabeth Pérez-Valenciano²  JesúsM. Sanz²  Miguel Saceda³  Pilar García-Morales³  VíctorM. Barberá³ 

[1] Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), C/Maestro Alonso, 10, 03005 Alicante, Spain;

[2] 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;

[3] 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;

关键词: magnetic nanoparticle;    cancer therapy;    reactive oxygen species;    oxidative damage;    cytotoxicity;    choline-binding proteins;   

DOI  :  10.3390/biom10020222

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown