**3. Antioxidants and cancer**

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 disease and it develops in three stages. These stages are initiation, promotion, and progression [21]. Cells suffer damage with any endogenous or exogenous effects. Defects or mutations accumulate in the cell with these effects. The main effects are listed below [22]:

The main objectives of oncological treatment are increasing life-quality and extending survival time. When these objectives are considered, antioxidant supplementation brings to

Antioxidant Supplementation during Glioma Therapy: Friend or Foe?

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In accordance with these questions, lots of experimental and clinical studies were carried out to prove the role of antioxidants in cancer therapy [16, 24–30]. Results obtained from these studies were variable. This variation is basically related to cancer type and cancer grade. ROS-

Gliomas are a class of primary central nervous system tumors and they originated from glial cells [1]. Glial progenitor cells have different subtypes: astrocyte, oligodendrocyte, and ependyma. In general, the classification of gliomas is based on these cell types [4]. The most detailed classification belongs to WHO. WHO suggests that four different grades (I–II–III–IV) are described for gliomas according to morphological and histological features [1]. Besides these features, some molecular and genetic features (epidermal growth factor upregulation,

isocitrate dehydrogenase 1/2 mutations, p53 mutations, etc.) also alter the grading [2].

Tumor grade and class are major factors to determine the therapy options. Surgery, chemotherapy, and radiotherapy are preferred to treat the gliomas. After surgery, chemotherapy or radiotherapy is applied. For the glioma treatment, the most frequently encountered problems are the blood-brain barrier and drug resistance [31]. The blood-brain barrier is a control mechanism in relation to the transition of ions, molecules, and cells between the blood and brain. If a drug does not pass through the blood-brain barrier, it cannot reach the brain

The second problem is drug resistance [33]. Temozolomide is the most common chemotherapeutic agent for gliomas. It is an alkylating agent [34]. In case of elevated levels of O6

guanine DNA methyltransferase expression, temozolomide meets with resistance [35]. On the other hand, increased levels of antioxidant response system SLC7A11 triggered the drug

Over the past decades, antioxidant supplementation becomes a necessity for cancer treatment. Basically, antioxidants use to eliminate the elevated levels of ROS, but cancer in question nothing is understandable. For this reason, researchers have carried out some studies. Understanding the beneficial or harmful roles of antioxidants in cancer treatment is essential. Further to that understanding of ROS effects in terms of cancer progression is really important. ROS is a reason


• Are some of side-effects related to current therapy eliminated by antioxidants?

cancer relationship and antioxidant junction points are described **Figure 1**.

An antioxidant-cancer relationship is deeply discussed next part in terms of glioma.

mind some questions. If clinicians add antioxidants to therapy:

• Does the success of therapy increase or decrease?

**4. Antioxidants and gliomas relationship**

cells [32].

resistance [31].

• Does antioxidant supplementation affect survival rates?


Aforementioned before ROS cause some pathological situations due to their reactive features [10]. They react with nucleic acids, proteins, lipids, and carbohydrates. As a result of this interaction, it is possible that cancer development may be from one cell. ROS may take a role any stages of carcinogenesis [7]. Proven roles of ROS on cancer progression [23]:


**Figure 1.** ROS-cancer relationship and antioxidant junction points.

The main objectives of oncological treatment are increasing life-quality and extending survival time. When these objectives are considered, antioxidant supplementation brings to mind some questions. If clinicians add antioxidants to therapy:

• Does the success of therapy increase or decrease?

disease and it develops in three stages. These stages are initiation, promotion, and progression [21]. Cells suffer damage with any endogenous or exogenous effects. Defects or muta-

Aforementioned before ROS cause some pathological situations due to their reactive features [10]. They react with nucleic acids, proteins, lipids, and carbohydrates. As a result of this interaction, it is possible that cancer development may be from one cell. ROS may take a role

any stages of carcinogenesis [7]. Proven roles of ROS on cancer progression [23]:

• ROS activate the PI3K/AKT/mTOR and MAPK/ERK mitogenic signaling pathways.

• ROS promote cell migration via invadopodia formation in vitro.

tions accumulate in the cell with these effects. The main effects are listed below [22]:

• Environmental factors,

234 Glioma - Contemporary Diagnostic and Therapeutic Approaches

• Inherited genetic diseases,

• Reactive oxygen species (ROS).

• Some genetic alterations are generated by ROS.

**Figure 1.** ROS-cancer relationship and antioxidant junction points.

• Lifestyle, • Infections, • Mutations,

• Viruses


In accordance with these questions, lots of experimental and clinical studies were carried out to prove the role of antioxidants in cancer therapy [16, 24–30]. Results obtained from these studies were variable. This variation is basically related to cancer type and cancer grade. ROScancer relationship and antioxidant junction points are described **Figure 1**.

An antioxidant-cancer relationship is deeply discussed next part in terms of glioma.
