Role of redox status in development of Glioblastoma
Por:
Salazar-Ramiro A., Ramírez-Ortega D., de La Cruz V.P., Hérnandez-Pedro N.Y., González-Esquivel D.F., Sotelo J., Pineda B.
Publicada:
1 ene 2016
Resumen:
Glioblastoma multiforme (GBM) is a highly aggressive neoplasia, prognosis remains dismal, and current therapy is mostly palliative. There are no known risk factors associated with gliomagenesis; however, it is well established that chronic inflammation in brain tissue induces oxidative stress in astrocytes and microglia. High quantities of reactive species of oxygen into the cells can react with several macromolecules, including chromosomal and mitochondrial DNA, leading to damage and malfunction of DNA repair enzymes. These changes bring genetic instability and abnormal metabolic processes, favoring oxidative environment and increase rate of cell proliferation. In GBM, a high metabolic rate and increased basal levels of reactive oxygen species play an important role as chemical mediators in the regulation of signal transduction, protecting malignant cells from apoptosis, thus creating an immunosuppressive environment. New redox therapeutics could reduce oxidative stress preventing cellular damage and high mutation rate accompanied by chromosomal instability, reducing the immunosuppressive environment. In addition, therapies directed to modulate redox rate reduce resistance and moderate the high rate of cell proliferation, favoring apoptosis of tumoral cells. This review describes the redox status in GBM, and how this imbalance could promote gliomagenesis through genomic and mitochondrial DNA damage, inducing the pro-oxidant and proinflammatory environment involved in tumor cell proliferation, resistance, and immune escape. In addition, some therapeutic agents that modulate redox status and might be advantageous in therapy against GBM are described. © 2016 Salazar-Ramiro, Ramírez-Ortega, Pérez de la Cruz, Hérnandez-Pedro, González-Esquivel, Sotelo and Pineda.
Filiaciones:
Salazar-Ramiro A.:
Neuroimmunology and Neuro-Oncology Unit, National Neurology and Neurosurgery Institute (INNN), Mexico
Ramírez-Ortega D.:
Neurochemistry Unit, National Neurology and Neurosurgery Institute (INNN), Mexico
de La Cruz V.P.:
Neurochemistry Unit, National Neurology and Neurosurgery Institute (INNN), Mexico
Hérnandez-Pedro N.Y.:
Experimental Oncology Laboratory, National Cancer Institute, Mexico
González-Esquivel D.F.:
Neurochemistry Unit, National Neurology and Neurosurgery Institute (INNN), Mexico
Sotelo J.:
Neuroimmunology and Neuro-Oncology Unit, National Neurology and Neurosurgery Institute (INNN), Mexico
Pineda B.:
Neuroimmunology and Neuro-Oncology Unit, National Neurology and Neurosurgery Institute (INNN), Mexico
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