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

Autor: P. Garcia-Morales, Maria Fuentes-Baile, Miguel Saceda, Víctor Manuel Barberá, Camino de Juan Romero, Elizabeth Pérez-Valenciano, María Paz Ventero, Cristina Alenda, Jesús Sanz
Přispěvatelé: Instituto de Salud Carlos III, Asociación de Mujeres afectadas por Cáncer de mama de Elche y comarca, Ministerio de Economía, Industria y Competitividad (España), Consejo Superior de Investigaciones Científicas (España), Fuentes-Baile, María [0000-0003-3653-2407], Ventero, María Paz [0000-0003-1979-0949], Sanz, Jesús M. [0000-0002-4421-9376], de Juan Romero, Camino [0000-0001-7890-8447], Barberá, Victor M. [0000-0002-4012-6973], Alenda, Cristina [0000-0002-0560-1759], Saceda, Miguel [0000-0002-1564-3602], Fuentes-Baile, María, Ventero, María Paz, Sanz, Jesús M., de Juan Romero, Camino, Barberá, Victor M., Alenda, Cristina, Saceda, Miguel
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Cancer therapy
Colorectal cancer
Biopsy
Poly (ADP-Ribose) Polymerase-1
Apoptosis
oxidative damage
Calcium mobilization
Calcium in biology
lcsh:Chemistry
AIF
Necrotic-like cell death
RNA
Small Interfering
lcsh:QH301-705.5
Choline binding
Spectroscopy
Membrane Potential
Mitochondrial
reactive oxygen species
Cell Death
Chemistry
apoptosis
Apoptosis Inducing Factor
N-Acetylmuramoyl-L-alanine Amidase
General Medicine
necrotic-like cell death
Computer Science Applications
Gene Expression Regulation
Neoplastic
cancer therapy
Mitochondrial membrane potential
Colorectal Neoplasms
HT29 Cells
D-Amino-Acid Oxidase
Programmed cell death
Antineoplastic Agents
Context (language use)
PARP-1
Article
Catalysis
Inorganic Chemistry
Necrosis
mitochondrial membrane potential
Cell Line
Tumor
Oxidative damage
medicine
Humans
Physical and Theoretical Chemistry
Molecular Biology
Inflammation
Gene Expression Profiling
Organic Chemistry
NF-kappa B p50 Subunit
Cancer
medicine.disease
Pancreatic Neoplasms
Oxidative Stress
lcsh:Biology (General)
lcsh:QD1-999
calcium mobilization
Cell culture
Cancer research
Calcium
Reactive oxygen species
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 22
Digital.CSIC. Repositorio Institucional del CSIC
instname
International Journal of Molecular Sciences, Vol 21, Iss 8522, p 8522 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21228522
Popis: 23 p.-11 fig.
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.
This research was funded by Spanish Instituto de Salud Carlos III, grant number PI01202025, and donations from Association of women affected by breast cancer in Elche and the region (AMACMEC) to M.S., Miguel Servet Program from Instituto de Salud Carlos III (CP19/00095) to C.d.J.R. and grants from the Spanish Ministry of Economy, Industry and Competitiveness, grant numbers BIO2013-47684-R and BIO2016-79323-R, and the RETICS-FEDER RICET, RD16/0027/0010, to J.M.S. The CIBER of Enfermedades Respiratorias (CIBERES) is an initiative of the Spanish Instituto de Salud Carlos III and Spanish National Research Council (CSIC Grant 201820I132).
Databáze: OpenAIRE
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