Cell Death Mechanisms Induced by CLytA-DAAO Chimeric Enzyme in Human Tumor Cell Lines

International Journal of Molecular Sciences

卷:21

JesúsM. Sanz¹  Elizabeth Pérez-Valenciano²  Pilar García-Morales²  Camino de Juan Romero³  Miguel Saceda³  VíctorM. Barberá³  María Fuentes-Baile³  Cristina Alenda⁴  MaríaP. Ventero⁴ 

[1] Centro de Investigaciones Biológicas Margarita Salas (Consejo Superior de Investigaciones Científicas) and Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), C/Ramiro de Maeztu 9, 28040 Madrid, 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, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO), Hospital General Universitario de Elche, Camí de l’Almazara 11, 03203 Elche (Alicante), Spain;

[4] Unidad de Investigación, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Hospital General Universitario de Alicante, C/Maestro Alonso 10, 03010 Alicante, Spain;

关键词: cancer therapy;    reactive oxygen species;    oxidative damage;    mitochondrial membrane potential;    calcium mobilization;    PARP-1;   

DOI  :  10.3390/ijms21228522

来源: DOAJ

【 摘 要 】

The combination of the choline binding domain of the amidase N-acetylmuramoyl-L-alanine (CLytA)-D-amino acid oxidase (DAAO) (CLytA-DAAO) and D-Alanine induces cell death in several pancreatic and colorectal carcinoma and glioblastoma cell lines. In glioblastoma cell lines, CLytA-DAAO-induced cell death was inhibited by a pan-caspase inhibitor, suggesting a classical apoptotic cell death. Meanwhile, the cell death induced in pancreatic and colon carcinoma cell lines is some type of programmed necrosis. In this article, we studied the mechanisms that trigger CLytA-DAAO-induced cell death in pancreatic and colorectal carcinoma and glioblastoma cell lines and we acquire a further insight into the necrotic cell death induced in pancreatic and colorectal carcinoma cell lines. We have analyzed the intracellular calcium mobilization, mitochondrial membrane potential, PARP-1 participation and AIF translocation. Although the mitochondrial membrane depolarization plays a crucial role, our results suggest that CLytA-DAAO-induced cell death is context dependent. We have previously detected pancreatic and colorectal carcinoma cell lines (Hs766T and HT-29, respectively) that were resistant to CLytA-DAAO-induced cell death. In this study, we have examined the putative mechanism underlying the resistance in these cell lines, evaluating both detoxification mechanisms and the inflammatory and survival responses. Overall, our results provide a better understanding on the cell death mechanism induced by CLytA-DAAO, a promising therapy against cancer.

【 授权许可】

Unknown