*4.1.2. Animal studies*

for cancer progression, but in course of cancer development increased levels of ROS might be a cell-death option. Moreover, increased levels of ROS alter the cell signaling in cancer cell in consequence of acting as secondary messengers [17]. For instance, Akt overexpression is frequently showed in gliomas, and protein kinase C (PKC) activation stimulates some molecules like Akt, MAPK.All these molecules are under the control by cellular redox state [36]. As a result of these features, ROS antioxidants can be provided new approaches in order to treat glioma. It is still

Accumulating data suggest two different approaches regarding antioxidant consumption. One is that antioxidants make tumor cells resistance against chemotherapy or radiotherapy and the survival rates are decreased. On the other hand, the second is that antioxidants protect the normal cells from oxidative damage and they are decreased side effects of therapy and provide better survival [8, 37, 38]. The next part of this chapter is related to evidence regarding

Gliomagenesis is still an unknown, incurable, and lethal process. New and effective treatment strategies are the necessity and understanding the gliomagenesis is essential in order to develop these options. Experimental evidence indicates that antioxidants are sometimes

In 1995, Zhu et al. carried out a study to clarify the effects of selenium on rat and human glioblastoma multiforme cell lines. They used sodium selenite and showed that selenium had anti-proliferative effects on both A172 human glioblastoma cells and C6 rat glioblastoma cells,

In 1997, Vartak et al. showed that some polyunsaturated fatty acids: gamma-linoleic acid (GLA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) supplementations increased the radiosensitivity and also radiation response on 36B10 rat astrocytoma cells [40]. In 1998, Vartak et al. compared the effects of GLA and linoleic acid (LA) on 36B10 malignant rat astrocytoma and normal rat astrocytes. They found that GLA was cytotoxic for astrocytoma cells, but not astrocytes. LA was not effective for both cells. It suggested that GLA might

cysteine, NAC) on U373-MG astrocytoma cell line. They observed that tumor cell prolifera-

In the beginning 2000s, the first study came from Rooprai et al. They checked some antiinvasive and anti-proliferative agents: swainsonine, captopril, tangeretin, and nobiletin on four different glioma cell lines: ependymoma, oligoastrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. Firstly, they observed that each cell line showed difference response

O2 [25]. O2

) and antioxidant (N-acetyl-

an unknown and questionable area for the researchers.

236 Glioma - Contemporary Diagnostic and Therapeutic Approaches

these two opinions.

*4.1.1. In vitro studies*

**4.1. Evidence-based studies**

friend, and in some cases, they are the foe.

be used for astrocytoma treatment [41].

but it was more effective on human glioblastoma cells [39].

In 1999, Arora-Kuruganti et al. examined roles of oxidant (H<sup>2</sup>

tion was inhibited by NAC. NAC also induced H2

In 1981, Newell et al. used a mixture of vitamins C and B12 in high dose on rats with glioma. They observed no difference in survival time between experimental and control groups [49].

In 1989, Wang et al. showed that retinoids (retinal, retinoic acid, retinyl acetate, and retinyl palmitate) and carotenoids (beta-carotene, lycopene, and crocetin) inhibited the tumor growth in C6 glioma cells inoculated rats [50].

A study regarding naringenin using was carried out on rats by Sabarinathan et al. [30]. With supplementation of naringenin in glioma induced rats the status of lipid peroxidation was decreased, on the contrary antioxidant status increased. Besides this, naringenin also modulate the glial-tumor cell proliferation [30].

In 2013, Perez de la Ossa et al. examined that Δ<sup>9</sup> -tetrahidrocannabinol (THC) and cannabidiol (CBD) effects on tumor growth in xenograft glioblastoma multiforme model. THC and CBD loaded on microparticles and delivered locally. At the end of the study they found that THC and CBD stimulated apoptosis and induced cell proliferation and angiogenesis [51].

In 2013, Hervouet et al. found that using SUVIMAX-like diet (supplementation en vitamins et minéraux antioxydants), which was enriched with beta carotene, alpha tocopherol, vitamin C, zinc, and sodium selenite, was delayed the clinical signs on ethyl-nitrosourea induced glioma rat model, but gliomagenesis occurred. This diet just decreased the tumor aggressiveness [52].

of antioxidant supplementation can determine appropriate clinical trials. Antioxidants' interference in chemotherapeutic mechanisms is still unknown and clinical fails of therapeutic

Antioxidant Supplementation during Glioma Therapy: Friend or Foe?

http://dx.doi.org/10.5772/intechopen.77079

239

In summary, antioxidant cancer therapy remains incapable. ROS scavengers must give place to antioxidant inhibitors. ROS-related cell death mechanism is a novel approach to provide the selective cell death. Further investigations will need to see the effectiveness of pro-oxidant

Department of Molecular Medicine, Graduate School of Health Sciences, Dokuz Eylul

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approaches regarding redox modulation are obvious.

Address all correspondence to: duyguharmanci@gmail.com

**19**(suppl\_5):v1-v88. DOI: 10.1093/neuonc/nox158

cancer therapy.

**Author details**

Duygu Harmanci

**References**

University, Izmir, Turkey

10.1038/nrdp.2015.17

In 2017, prolonged survival time was showed treatment with coptis chinensis on glioma induced mice model by Li et al. [53].

Combination of berbamine and paxitaxel was delayed the development of tumor U87 xenograft model [47].
