**1. Introduction**

Central nervous system tumors start in the brain or spinal cord [1]. The common symptoms of these tumors are headache, seizures, weakness, nausea, vomiting, and altered mental status [1, 2]. Gliomas are one of the most common primary brain tumors, which are originated from glial cells. In general, gliomas are classified astrocytoma, oligodendrogliomas, and ependymomas. According to World Health Organization (WHO), the histological classification of gliomas consists of astrocytoma, oligodendroglioma, oligoastrocytoma (low-grade gliomas)

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

and anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, anaplastic ependymoma, and glioblastoma (high-grade gliomas) [1–4]. The histological type of the tumor is the most significant thing to determine the treatment option [2].

Antioxidants are present in plant-based foods, for instance, some types of vegetables and fruits: wine, blueberry, different types of tea, grape, and so on [5, 6]. The main role of antioxidants is prevention of oxidants' harmful effects to human body. Principle regarding oxidant-antioxidant is related to a balance [7]. This balance's side determines the human body reaction. In case of elevated oxidant levels in organism body homeostasis is lost and oxidative stress occurs. Loss of this balance and oxidative stress lead some pathological situations: cancer, neurodegenerative diseases, cardiovascular diseases, immunological diseases, and so on [8–10]. In terms of these diseases with the antioxidant supplementation, cell damage can be fixed.

In this chapter, two different stories will be told and these stories will be turned one story. We will discuss some of the basic concepts of antioxidants, antioxidant systems and antioxidants supplementation and explain how antioxidant supplementation can help with the cancer therapy, especially glioma therapy. Experimental studies are summarized and present evidences are collected under three headings: in vitro studies, animal studies, and clinical trials.

reactive-nitrogen species [6, 14]. These molecules can get involved with oxidant molecules, but all oxidants are not free radicals. They produce endogenously or with some exogenous sources' effects [9, 10]. Some endogenous and exogenous sources are shown in **Table 2**.

UV

Smoking

Ozone exposure Hyperoxia

Burning organic foods

Antioxidant Supplementation during Glioma Therapy: Friend or Foe?

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Ionizing radiation Air pollutants Heavy metal ions

**Endogenous sources Exogenous sources**

Normal cellular metabolism • Electron transport chain • Neutrophils, macrophages • Mitochondrial cytochrome oxidase

• Smooth muscle cells • Cortisol, catecholamine • Immune system cells

**Table 2.** Endogenous and exogenous sources of ROS.

In human body, antioxidant systems are present to avoid cell damage due to free radicals. These antioxidant systems include a few enzymes for this reason they are called enzymatic antioxidants [9–11, 14]. The definition of antioxidant that it is a molecule reacts with free radicals and neutralizes them [6]. Except enzymatic antioxidants, generally, they occur naturally in foods, especially plant-based foods [15]. For instance, resveratrol is a very popular antioxidant in recent years, and it is found in grape, raspberry, blueberry, wine, and so on [16]. The most known non-enzymatic antioxidants are low-molecular-weight compounds such as vitamin C, vitamin E, beta-carotene, catechins, lycopene, glutathione, and coenzyme Q [5, 12, 17]. In summary, the story starts with oxygen and develops free radicals and stable molecules (DNA, protein, lipids, carbohydrates, etc.). Antioxidants are the good cops and they get involved the free radicals. In normal conditions, this is acceptable as happy ending. In terms of biological perspective, in course of normal metabolism energy production starts with consumption of oxygen and food nutrients. Oxygen and food enter the cell and mitochondria start to produce adenosine triphosphate (ATP). Free radicals form during cell's energy production. These free radicals are neutralized by antioxidant enzyme systems (superoxide dismutase, catalase, glutathione peroxidase, etc.) and non-enzymatic antioxidants [6]. In the presence of any pathological conditions, ROS are highly produced and although antioxidant enzyme systems and antioxidants try to eliminate them to protect the cell, they remain incapable. Redox balance breaks down, oxidative stress increases, and antioxidant levels decrease

[14]. In terms of cancer, ROS imbalance is one of the hallmarks of cancer [18].

Cancer is a malign disease, which is characterized by abnormal cell proliferation [19, 20]. The uncontrolled situation in the cell is a result of endogenous or exogenous effects. According to multistep carcinogenesis theory, cancer originated from one cell, so cancer is a monoclonal

**3. Antioxidants and cancer**
