**Abstract**

Antioxidant compounds are thought to prevent and treat diseases, especially cancer, under any circumstances. For this purpose, nature-based antioxidants nowadays are being commonly used to prevent and treat diseases. Indeed, phenolic compounds found in medicinal plants have opened a new horizon to prevent and treat diseases because of having antioxidant properties. However, some recent studies have reported that antioxidants are not absolute anticancer compounds and certain drugs have been reported to reduce levels of reactive oxygen species (ROS) in the cancer cells, i.e., their main action mechanism. It has been argued that increasing levels of ROS cause an increase in apoptosis rate and therefore can be considered an approach to treat fatal and hard-to-treat cancers. This chapter seeks to partly explain the role of ROS in progression or inhibition of cancer growth in addition to the role of antioxidants in preventing and treating this disease.

**Keywords:** reactive oxygen species, antioxidant, cancer, apoptosis

#### **1. Introduction**

Cancer kills many people worldwide every year. Even in developed countries such as the United States, the rate of mortalities of cancer is high yet [1]. Although nowadays cancer therapy has improved, since complete recovery of cancer patients following a single treatment is quite difficult, a multidisciplinary approach combined with surgery, chemotherapy, radiotherapy, and immunotherapy is usually utilized [2, 3]. However, some of these approaches cause several severe side effects in patients. Moreover, for many patients, current therapeutic approaches are successful only in delaying the time to disease progression rather than affecting long-term survival rates [4].

Many previous studies have shown that antioxidant supplementations are useful in cancer treatment [5]. An antioxidant substance in the cell is present at low concentrations and significantly reduces or prevents oxidation of the oxidizable substrates [6]. The researchers have evaluated highly complex antioxidant to protect the cells of the body against free radical damages [4]. However, some recent studies have reported that decreasing levels of cells' oxidants, as reactive oxygen species (ROS) increase, causes increase in apoptosis rate and therefore can be considered an approach to treat fatal and hard-to-treat cancers.

This chapter seeks to partly explain the role of ROS in progression or inhibition of cancer growth in addition to the role of antioxidants in preventing and treating this disease.

#### **2. Oxidative stress in cancer**

Among many factors that cause cancer, oxidative stress is one of the most principal and well-studied events that gives elevation to the conditions leading to tumor onset and progression [7, 8]. The oxidative stress and chronic inflammation processes are tightly coupled, and the failure to block these processes could result in genetic/epigenetic changes that drive the initiation of carcinogenesis [9]. Oxidative stress as an imbalance between the production and elimination of ROS causes excessive oxidative damage to macromolecules, cells, and tissues [10]. Oxidative/ nitrosative stress-induced peroxidation of membrane lipids can be very damaging because it leads to alterations in the biological properties of the membrane, such as the degree of fluidity, and can lead to inactivation of membrane-bound receptors or enzymes, which in turn may disable normal cellular function and increment tissue permeability [11]. The main outcome of oxidative/nitrosative stress is damage to lipids, nucleic acids, and proteins that can induce a variety of cellular responses through generation of reactive species or can compromise cell health and viability, finally causing cell death via apoptosis or necrosis [5, 12].

#### **3. Reactive oxygen species (ROS)**

Free radicals are known as "any chemical species capable of independent existence that contains one or more unpaired electrons" [13]. Reactive oxygen species (ROS) are free radicals which are correlated with the oxygen atom (O) or their equivalents and have stronger reactivity with other molecules, rather than with O2 [14]. When an imbalance between free radical and reactive metabolite production occurred, ROS are formed and can potentially exhibit a negative effect on the organism [15]. ROS is a collective term that includes the superoxide anion (O2 <sup>−</sup>), hydrogen peroxide (H2O2), and hydroxyl radical (HO˙) [14]. Radical formation in the body occurs via several mechanisms, involving both endogenous and environmental factors [11].

#### **4. ROS in cancer**

Cancer is a multistage process defined by initiation, promotion, and progression [16, 17], and oxidative stress interacts with all three stages. A little increase in the ROS level may cause a transient alteration in the cellular level, while a severe increase in ROS may result to irreversible oxidative damage and lead to cell death [18]. ROS can also promote carcinogenesis by inducing pro-oncogenic signaling pathways and DNA mutations. For instance, ROS may stimulate the phosphorylation of mitogen-activated protein kinase (MAPK), JUN N-terminal kinase (JNK) activation, cyclin D1 expression, and extracellular signal-regulated kinase (ERK), all of which are related to growth of tumor cells and survival [19].

Cancer cells generate ROS more abundantly than normal cells and cause elevated oxidative stress [20]. ROS can induce tumorigenicity and promote tumor progression via inducing DNA damage [21]. ROS induces gene mutations and structural changes in the DNA and results in DNA damage during the early stage

**175**

sword.

**Figure 1.**

cells from oxidative damage.

*Antioxidants as a Double-Edged Sword in the Treatment of Cancer*

of tumorigenicity. In addition to, ROS can increase cell proliferation and decrease apoptosis via modifying second-messenger systems, causing abnormal gene expression, and blocking cell communications. Finally, oxidative stress can add DNA alterations to initiate cell population and promote cancer progression [22].

ROS might function as a double-edged sword (**Figure 1**). A moderate increase of ROS may promote cell proliferation and survival. However, when the increase of ROS reaches a certain level (the toxic threshold), it can overwhelm the antioxidant capacity of the cells and result in cell death [23]. It is long thought that antioxidants can remove the ROS that is produced in normal cellular processes and can protect

Reactive oxygen species (ROS) can promote cellular processes to cancer. In addition, they can induce apoptosis. Actually, ROS might function as a double-edged

Antioxidants as chemicals that interact with neutralized free radicals can prevent them from causing damages. Antioxidants divide to two main subgroups including enzymatic and nonenzymatic antioxidants. Catalase, superoxide dismutase, and glutathione peroxidases are some of the most important enzymatic antioxidants [11]. Catalase (EC 1.11.1.6) as the first antioxidant enzyme was to be characterized and catalyzes conversion of hydrogen peroxide to water and oxygen. Superoxide dismutase (EC 1.15.1.1) is one of the most potent intracellular enzymatic antioxidants that catalyzes the conversion of superoxide anions to dioxygen and hydrogen peroxide. Glutathione peroxidases catalyze the oxidation of glutathione

**5. Antioxidants as a double-edged sword in cancer**

*Relation between ROS actions with promoting and fighting cancer [23].*

*DOI: http://dx.doi.org/10.5772/intechopen.85468*

*Antioxidants as a Double-Edged Sword in the Treatment of Cancer DOI: http://dx.doi.org/10.5772/intechopen.85468*

**Figure 1.**

*Antioxidants*

this disease.

**2. Oxidative stress in cancer**

This chapter seeks to partly explain the role of ROS in progression or inhibition of cancer growth in addition to the role of antioxidants in preventing and treating

Among many factors that cause cancer, oxidative stress is one of the most principal and well-studied events that gives elevation to the conditions leading to tumor onset and progression [7, 8]. The oxidative stress and chronic inflammation processes are tightly coupled, and the failure to block these processes could result in genetic/epigenetic changes that drive the initiation of carcinogenesis [9]. Oxidative stress as an imbalance between the production and elimination of ROS causes excessive oxidative damage to macromolecules, cells, and tissues [10]. Oxidative/ nitrosative stress-induced peroxidation of membrane lipids can be very damaging because it leads to alterations in the biological properties of the membrane, such as the degree of fluidity, and can lead to inactivation of membrane-bound receptors or enzymes, which in turn may disable normal cellular function and increment tissue permeability [11]. The main outcome of oxidative/nitrosative stress is damage to lipids, nucleic acids, and proteins that can induce a variety of cellular responses through generation of reactive species or can compromise cell health and viability,

Free radicals are known as "any chemical species capable of independent existence that contains one or more unpaired electrons" [13]. Reactive oxygen species (ROS) are free radicals which are correlated with the oxygen atom (O) or their equivalents and have stronger reactivity with other molecules, rather than with O2 [14]. When an imbalance between free radical and reactive metabolite production occurred, ROS are formed and can potentially exhibit a negative effect on the organism [15]. ROS is a collective term that includes the superoxide anion

<sup>−</sup>), hydrogen peroxide (H2O2), and hydroxyl radical (HO˙) [14]. Radical formation in the body occurs via several mechanisms, involving both endogenous

Cancer is a multistage process defined by initiation, promotion, and progression [16, 17], and oxidative stress interacts with all three stages. A little increase in the ROS level may cause a transient alteration in the cellular level, while a severe increase in ROS may result to irreversible oxidative damage and lead to cell death [18]. ROS can also promote carcinogenesis by inducing pro-oncogenic signaling pathways and DNA mutations. For instance, ROS may stimulate the phosphorylation of mitogen-activated protein kinase (MAPK), JUN N-terminal kinase (JNK) activation, cyclin D1 expression, and extracellular signal-regulated kinase (ERK),

all of which are related to growth of tumor cells and survival [19].

Cancer cells generate ROS more abundantly than normal cells and cause elevated oxidative stress [20]. ROS can induce tumorigenicity and promote tumor progression via inducing DNA damage [21]. ROS induces gene mutations and structural changes in the DNA and results in DNA damage during the early stage

finally causing cell death via apoptosis or necrosis [5, 12].

**3. Reactive oxygen species (ROS)**

and environmental factors [11].

**4. ROS in cancer**

**174**

(O2

*Relation between ROS actions with promoting and fighting cancer [23].*

of tumorigenicity. In addition to, ROS can increase cell proliferation and decrease apoptosis via modifying second-messenger systems, causing abnormal gene expression, and blocking cell communications. Finally, oxidative stress can add DNA alterations to initiate cell population and promote cancer progression [22].

ROS might function as a double-edged sword (**Figure 1**). A moderate increase of ROS may promote cell proliferation and survival. However, when the increase of ROS reaches a certain level (the toxic threshold), it can overwhelm the antioxidant capacity of the cells and result in cell death [23]. It is long thought that antioxidants can remove the ROS that is produced in normal cellular processes and can protect cells from oxidative damage.

Reactive oxygen species (ROS) can promote cellular processes to cancer. In addition, they can induce apoptosis. Actually, ROS might function as a double-edged sword.
