Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL). C/Maestro Alonso, 10. 03005 Alicante, Spain.
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.
Biomolecules. 2020 Feb 3;10(2):222. doi: 10.3390/biom10020222.
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.
D-氨基酸氧化酶（DAAO）催化 D-氨基酸的氧化，生成过氧化氢，这是活性氧物种的潜在产生者。在这项研究中，我们使用了 CLytA-DAAO 嵌合体，无论是游离的还是结合到磁性纳米颗粒上，都可以对抗结肠癌细胞系、胰腺腺癌细胞系和神经胶质瘤细胞系。我们发现，该酶诱导了大多数测试细胞系的细胞死亡，并且当它固定在纳米颗粒上时，其效率显著提高。我们还在非肿瘤细胞中测试了这种酶疗法，发现没有诱导细胞死亡，或者明显低于肿瘤细胞。触发细胞死亡的机制显然是神经胶质瘤细胞系中的经典细胞凋亡途径，而在结肠和胰腺癌细胞系中，CLytA-DAAO 诱导的细胞死亡是坏死。我们的结果证明了一种基于磁性纳米颗粒传递 CLytA-DAAO 的酶疗法可以作为一种有效的癌症治疗方法，此外，它还可以用作其他治疗方法（如表观遗传治疗、放射治疗和基于 DNA 修复的治疗）的增强剂。
