Role of Inflammation and Oxidative Stress Mediators in Gliomas

Abstract

Gliomas are the most common primary brain tumors of the central nervous system. Despite relevant progress in conventional treatments, the prognosis of such tumors remains almost invariably dismal. The genesis of gliomas is a complex, multistep process that includes cellular neoplastic transformation, resistance to apoptosis, loss of control of the cell cycle, angiogenesis, and the acquisition of invasive properties. Among a number of different biomolecular events, the existence of molecular connections between inflammation and oxidative stress pathways and the development of this cancer has been demonstrated. In particular, the tumor microenvironment, which is largely orchestrated by inflammatory molecules, is an indispensable participant in the neoplastic process, promoting proliferation, survival and migration of such tumors. Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, as well as chemokines and prostaglandins, are synthesized by resident brain cells and lymphocytes invading the affected brain tissue. Key mediators of cancer progression include nuclear factor-kappaB, reactive oxygen and nitrogen species, and specific microRNAs. The collective activity of these mediators is largely responsible for a pro-tumorigenic response through changes in cell proliferation, cell death, cellular senescence, DNA mutation rates, DNA methylation and angiogenesis. We provide a general overview of the connection between specific inflammation and oxidative stress pathway molecules and gliomas. The elucidation of specific effects and interactions of these factors may provide the opportunity for the identification of new target molecules leading to improved diagnosis and treatment.

Comparison of Prooxidant-antioxidant Balance between Patients with High Grade Gliomas (IV) and Control Group

“…Some studies showed that activation of NF-KB factor protect some glioblastoma cells lines in vitro from chemotherapeutic agents. Data confirmed that tumor grade is associated to NF-KB activity and its activity increases progressively with malignancy (15). TGF-β2 is produced by human GBM cell lines and involved in the regulation of both suppression of anti-tumor immune surveillance and angiogenesis in malignant gliomas (16).…”

“…The creation of glioma tumor is a complex process involved neoplastic changes of cells, resistance to apoptosis, lack of cell cycle control and angiogenesis (12). Many studies showed that OS has a substantial role in these processes and modulation of OS can have a therapeutic potential in treatment (13)(14).…”

Function of neuronal nitric oxide synthase enzyme in temozolomide-induced damage of astrocytic tumor cells

“…Nitrite damages DNA strands, leading to various biochemical features observed in cancer cells such as changes in p53 activity and epidermal growth factor signaling (56)(57)(58). The increased NOS activity reported in glioma cells also contributes to oxidative stress (11). Similarly, inhibiting NOS enzymes by L-NAME resulted in a lower nitrite concentration in rat glioma tumor tissues with a decrease in tumor volume, which reinforces the benefits of reducing NOS activity in glioma cells (19,59).…”

“…The gas NO contributes to oxidative stress in astrocytic tumors (11). NO is often referred to as a toxic and reactive molecule.…”

“…The excessive levels of reactive oxygen species (ROS) may result in cell damage and apoptosis (10). However, ROS production, which includes nitric oxide (NO), may improve the survival, growth and neoplastic phenotype of various cancer cells, including astrocytic brain tumors (11,12).…”