**7. Advantages of using antioxidants as an anticancer approach**

In addition to the standard anticancer treatment options such as chemotherapy, radiotherapy, and surgery, several natural products due to their antioxidant activities have been identified to have a potential for cancer prevention [44] and treatment [45]**.**

In radiotherapy and chemotherapy, ROS and free radicals partly cause various adverse effects [46]. ROS generation causes various tissue or organ injuries; for example, doxorubicin and other anthracycline antibiotics are known to lead to cardiotoxicity [47]; cisplatin and other platinums lead to nephrotoxicity, ototoxicity, and peripheral neuropathy [48]; bleomycin leads to lung injury [49]; and alkylating agents cause DNA damage of drug-treated cells [50]. Tissue or organ injuries may also induce carcinogenesis [51]. Many previous studies reported that using antioxidants with these gold standard methods can significantly decrease these cellular damages. For instance, in one study that is reported by Askua et al., among the 49 studies, 46 examined the reduction of adverse effects by antioxidant supplementation; in 34 trials, possible reductions in chemotoxicities or radiotoxicities using antioxidant supplementation were reported; and only 1 RCT, using vitamin A, reported that supplementation possibly increased chemoinduced toxicities. The remaining 11 studies reported no significantly difference in toxicities between control and supplementation groups [51]. Further, the results of the Shanghai Breast Cancer Survival Study showed that consumption of multivitamins or vitamins such as C and E within 6 months of breast cancer diagnosis correlated with 18% decreased mortality and 22% decreased recurrence rate [52]. In addition, the Life After Cancer Epidemiology (LACE) cohort study results on effects of vitamins E and C and combination of carotenoid supplementation in breast cancer showed that vitamins E and C intake before and after breast cancer diagnosis was related to 22% reduced risk of all-cause mortality, 32% decreased breast cancer mortality, and 20% decreased recurrence risk [53].

#### **8. Future therapeutic perspectives**

We are approaching a new era wherein ROS biology and their effects in the physiopathology of cancer may be dissected with unprecedented detail, bringing potential therapeutic benefits derived from selective manipulations of cancer redox balance to be uncovered, paving the way to novel and exciting investigations in the

**179**

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

prove to be useful for more effectively killing cancer cells.

**9. Conclusion**

antioxidant.

fight against cancer [6]. Owing to the crucial roles of cancer stem cells in tumor initiation, disease recurrence, and drug resistance, the potential of using a redoxmodulating strategy to eliminate this subpopulation of malignant cells could have major implications in cancer treatment. Redox adaptation is an important concept that, to a large degree, explains the mechanisms by which cancer cells survive under persistent endogenous ROS stress and become resistant to certain anticancer agents. Targeting these biochemical properties of cancer cells with redox-modulating strategies is a feasible therapeutic approach that may enable therapeutic selectivity and overcome drug resistance. Also, Nrf2 is arguably the most important regulator of the expression of molecules that have antioxidant functions within the cell [13]. Nrf2 controls the expression of these enzymes and is considered to be a master regulator of intracellular antioxidant responses. An increased Nrf2 activity in normal cells is protective and beneficial against oxidative stress, but cancer cells harness the ability of Nrf2 to survive under stress conditions [14]. Nrf2 activators, such as bardoxolone methyl CDDO-Me, have shown anticancer activity preclinically and are currently being tested in clinical trials [15]. Moreover, glutathione (GSH) metabolism seems to be the main target of currently used anticancer drugs. Combinations of GSH inhibitors (or other antioxidant inhibitors) with radiotherapy or chemotherapeutic drugs that cause cell death induced by oxidative stress may

ROS/RNS protection in cancer is an important issue that attracts many scientists in recent years to discover the mechanism of action of various antioxidants. The idea that fruit and vegetable consumption alone is associated with a decreased risk of cancer is yet to be determined. This chapter shows that antioxidants, as previously reported, contribute to prevent and treat many types of cancer, but their anticancer effects are not absolute and depend on the time, amount, and conditions of their administration to treat different cancers. It is important that physicians make an integrated decision, based on the following consideration: (1) the background and state of the patient, (2) the antioxidant dosage and types, and (3) type of cancer and antitumor therapy. In addition, it is necessary to examine the safety and viability of antioxidants in pathological conditions and cancer therapy and that trials be performed with a single regimen, single type of cancer, and single

*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*

fight against cancer [6]. Owing to the crucial roles of cancer stem cells in tumor initiation, disease recurrence, and drug resistance, the potential of using a redoxmodulating strategy to eliminate this subpopulation of malignant cells could have major implications in cancer treatment. Redox adaptation is an important concept that, to a large degree, explains the mechanisms by which cancer cells survive under persistent endogenous ROS stress and become resistant to certain anticancer agents. Targeting these biochemical properties of cancer cells with redox-modulating strategies is a feasible therapeutic approach that may enable therapeutic selectivity and overcome drug resistance. Also, Nrf2 is arguably the most important regulator of the expression of molecules that have antioxidant functions within the cell [13]. Nrf2 controls the expression of these enzymes and is considered to be a master regulator of intracellular antioxidant responses. An increased Nrf2 activity in normal cells is protective and beneficial against oxidative stress, but cancer cells harness the ability of Nrf2 to survive under stress conditions [14]. Nrf2 activators, such as bardoxolone methyl CDDO-Me, have shown anticancer activity preclinically and are currently being tested in clinical trials [15]. Moreover, glutathione (GSH) metabolism seems to be the main target of currently used anticancer drugs. Combinations of GSH inhibitors (or other antioxidant inhibitors) with radiotherapy or chemotherapeutic drugs that cause cell death induced by oxidative stress may prove to be useful for more effectively killing cancer cells.
