Cell Death Mechanisms Induced by CLytA-DAAO Chimeric Enzyme in Human Tumor Cell Lines
Por:
Fuentes-Baile, M, Garcia-Morales, P, Perez-Valenciano, E, Ventero, M, Sanz, J, Romero, C, Barbera, V, Alenda, C and Saceda, M
Publicada:
1 nov 2020
Ahead of Print:
12 nov 2020
Resumen:
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.
Filiaciones:
Fuentes-Baile, M:
Hosp Gen Univ Elche, Fdn Fomento Invest Sanitaria & Biomed Comunidad V, Unidad Invest, Canal Almazara 11, Elche 03203, Alicante, Spain
Garcia-Morales, P:
Univ Miguel Hernandez, Inst Invest Desarrollo & Innovac Biotecnol Sanita, Avda Univ S-N, Elche 03202, Alicante, Spain
Perez-Valenciano, E:
Univ Miguel Hernandez, Inst Invest Desarrollo & Innovac Biotecnol Sanita, Avda Univ S-N, Elche 03202, Alicante, Spain
:
Hosp Gen Univ Alicante, Inst Invest Sanitaria & Biomed Alicante ISABIAL, Unidad Invest, C Maestro Alonso 10, Alicante 03010, Spain
Sanz, J:
CSIC, Ctr Invest Biol Margarita Salas, C Ramiro de Maeztu 9, Madrid 28040, Spain
Ctr Invest Biomed Red Enfermedades Resp CIBERES, C Ramiro de Maeztu 9, Madrid 28040, Spain
Romero, C:
Hosp Gen Univ Elche, Fdn Fomento Invest Sanitaria & Biomed Comunidad V, Unidad Invest, Canal Almazara 11, Elche 03203, Alicante, Spain
Univ Miguel Hernandez, Inst Invest Desarrollo & Innovac Biotecnol Sanita, Avda Univ S-N, Elche 03202, Alicante, Spain
Barbera, V:
Hosp Gen Univ Elche, Fdn Fomento Invest Sanitaria & Biomed Comunidad V, Unidad Invest, Canal Almazara 11, Elche 03203, Alicante, Spain
Hosp Gen Univ Elche, Unidad Genet Mol, Cami Almazara 11, Elche 03203, Alicante, Spain
:
Hosp Gen Univ Alicante, Inst Invest Sanitaria & Biomed Alicante ISABIAL, Unidad Invest, C Maestro Alonso 10, Alicante 03010, Spain
Saceda, M:
Hosp Gen Univ Elche, Fdn Fomento Invest Sanitaria & Biomed Comunidad V, Unidad Invest, Canal Almazara 11, Elche 03203, Alicante, Spain
Univ Miguel Hernandez, Inst Invest Desarrollo & Innovac Biotecnol Sanita, Avda Univ S-N, Elche 03202, Alicante, Spain
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