ROS and Brain Gliomas: An Overview of Potential and Innovative Therapeutic Strategies

Abstract

Reactive oxygen species (ROS) represent reactive products belonging to the partial reduction of oxygen. It has been reported that ROS are involved in different signaling pathways to control cellular stability. Under normal conditions, the correct function of redox systems leads to the prevention of cell oxidative damage. When ROS exceed the antioxidant defense system, cellular stress occurs. The cellular redox impairment is strictly related to tumorigenesis. Tumor cells, through the generation of hydrogen peroxide, tend to the alteration of cell cycle phases and, finally to cancer progression. In adults, the most common form of primary malignant brain tumors is represented by gliomas. The gliomagenesis is characterized by numerous molecular processes all characterized by an altered production of growth factor receptors. The difficulty to treat brain cancer depends on several biological mechanisms such as failure of drug delivery through the blood-brain barrier, tumor response to chemotherapy, and intrinsic resistance of tumor cells. Understanding the mechanisms of ROS action could allow the formulation of new therapeutic protocols to treat brain gliomas.

Isocitrate dehydrogenase‐mutant glioma: Evolving clinical and therapeutic implications

“…Finally, elevated 2HG levels have been implicated in the production of high levels of ROS, possibly because of disruption of the NAPD/NAPDH balance during 2HG generation. Elevated ROS has been linked to mutagenesis and tumorigenesis …”

Etiopathogenesis of Central Nervous System Gliomas

“…So that, unlike the conclusions of other researchers [17,[64][65][66][67][71][72][73][74][75][76], I believe that the etiopathogenesis of low-grade gliomas is related with decreasing arterial blood flow (mild to severe ischemia) and by contrast, increasing and prolonged hypoxia (hypoxic microenvironment) associated with environmental carcinogens of endogenous and exogenous origin [12,14,41,54,62,77,78]. We currently know that there is a tendency toward a higher incidence of gliomas in highly industrialized countries, where they use ionizing radiation and are exposed to chemicals [78] and moreover, that the female sex hormones play a role in the development of gliomas in women [15].…”

“…Then, the immature glial cells originated from the SVZ, in its process of proliferation and migration to the cerebral cortex and gray nuclei [16,17,46,[64][65][66][67]79] and in a state of prolonged hypoxia [17,35,80], they emit different biochemical responses in order to minimize the progressive damage caused cytotoxic hypoxia. First, ROS generation by the mitochondrial electron transport chain, leading to activation of hypoxia-inducible factor-1 (HIF-1) and HIF-2 through PHD inhibition; [72,80] After surgery he received diphenylhydantoin and carbamazepine for one year. The epileptic seizures disappeared.…”

“…ROS overproduction is a feature of cancer cells and plays several roles how to react with nucleic acids, lipids, carbohydrates, proteins and the resulting products inducing an imbalance in redox homeostasis [41,57,58,72]. The main linking substances able to relate inflammation to tumorigenesis through the oxidative/nitrosative stress, are prostaglandins and cytokines [61,83].…”

PTPN2 induced by inflammatory response and oxidative stress contributed to glioma progression

“…It has been reported that ROS participate in various pathways and can control cellular stability. 21 ROS may function as vital signaling molecules, which can favor tumorigenesis. [22][23][24] For example, restraining ROS in Listeria monocytogenes can promote glial cells apoptosis.…”