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

被引:23
作者
Fuentes-Baile, Maria [1 ,2 ]
Bello-Gil, Daniel [3 ]
Perez-Valenciano, Elizabeth [3 ]
Sanz, Jesus M. [3 ,4 ,5 ]
Garcia-Morales, Pilar [2 ,3 ]
Maestro, Beatriz [3 ,4 ,5 ]
Ventero, Maria P. [1 ]
Alenda, Cristina [1 ]
Barbera, Victor M. [2 ,6 ]
Saceda, Miguel [2 ,3 ]
机构
[1] Hosp Gen Univ Alicante, Inst Invest Sanitaria & Biomed Alicante ISABIAL, C Maestro Alonso 10, Alicante 03005, Spain
[2] Hosp Gen Univ Elche, Fdn Fomento Invest Sanitaria & Biomed Comunidad V, Unidad Invest, Cami Almazara 11, Elche 03203, Alicante, Spain
[3] Univ Miguel Hernandez, Inst Invest Desarrollo & Innovac Biotecnol Sanita, Avda Univ S-N, Elche 03202, Alicante, Spain
[4] CSIC, Ctr Invest Biol Margarita Salas, C Ramiro de Maeztu 9, E-28040 Madrid, Spain
[5] Ctr Invest Biomed Red Enfermedades Resp CIBERES, C Ramiro de Maeztu 9, Madrid 28040, Spain
[6] Hosp Gen Univ Elche, Unidad Genet Mol, Cami Almazara 11, Elche 03203, Alicante, Spain
关键词
magnetic nanoparticle; cancer therapy; reactive oxygen species; oxidative damage; cytotoxicity; choline-binding proteins; AMINO-ACID OXIDASE; MULTIDRUG-RESISTANCE; OXIDATIVE STRESS; TUMOR-CELLS; APOPTOSIS; PROTEINS; THERAPY; PURIFICATION; INDUCTION; ENZYMES;
D O I
10.3390/biom10020222
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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.
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页数:19
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