Ovarian tumors [173], among others [62, 174]. Another promising radiosensitizer is EGCG. This catechin has shown synergistic effects with radiation on radioresistant glioblastoma multiforme, multiple myeloma (IM-9), leukemia (K-562), and cancer cervix (HeLa) cells [125]. Moreover, a recent clinical trial showed that EGCG may improve the prognostic of breast cancer patients under radiotherapy [119]. Melatonin is one of the most studied antioxidants in recent years, both in in vitro and in vivo assays. As it was hypothesized by Vijayalaxmi et al. [175], melatonin may slow the order LY2510924 saturation of repair enzymes. This fact would lead to repairing the damage caused by oxidative stress and also would allow the use of higher doses of radiation in the treatment, making melatonin an ideal protective agent during radiotherapy. Although, in most studies, melatonin has been used at very high doses (it is not toxic up to 250 mg/kg), itOxidative Medicine and Cellular Longevity was found that its administration at low doses in mice, over a period of time (e.g., 0.1 mg/kg/day for 15 days before receiving radiation), appeared to be quite effective, so that the suitable dose of melatonin for humans in radiotherapy treatments is an issue that has to be investigated in more depth [126] (Table 2(b)). As for chemotherapy, there are numerous agents that induce cell death by oxidative stress either directly, leading to the disruption of redox signaling and ROS scavenging, or Ensartinib molecular weight indirectly by reducing intracellular levels of antioxidants and deactivating the cellular defense. Numerous articles have reported on many chemotherapeutic agents whose effects involve the induction of oxidative stress. Some of them are new molecules as Meroxest, a synthetic merosesquiterpene derivative of the trans-communic acid, plentiful in Cupressus sempervirens [176], or Jadomycin, which is synthesized by the bacteria Streptomyces venezuelae [177]. Other compounds are part of the current therapeutic repertoire, like oxaliplatin [178], bleomycin [179], gemcitabine [180, 181], cyclophosphamide [182], celecoxib [183], capecitabine [184, 185], bortezomib (a proteasome inhibitor, approved for the treatment of multiple myeloma) [186, 187], and arsenic trioxide (ATO). ATO, which is used in the treatment of acute promyelocytic leukemia (APL), can produce a loss of permeability of the outer mitochondrial membrane and impair the function of the respiratory chain, leading to an increase in superoxide anion [188?91]. However, many of the agents that induce oxidative stress have hardly any studies about the interaction between their antineoplastic activity and antioxidants. Then, we present the information about various antitumor drugs which have been selected according to their utility, therapeutic efficacy, and involvement in studies that were focused on the evaluation of the interaction with antioxidants during chemotherapy. Anthracyclines are antitumor antibiotics commonly used in chemotherapy. They have been linked to the generation of oxidative stress and increased ROS levels and could act as mediators of apoptosis by the activation of caspases 3 and 9 [192?94]. Doxorubicin (Adriamycin) is a widely anthracycline used in the treatment of various cancers, including solid breast and prostate tumors. It exerts its antitumor activity by inhibiting topoisomerase II and generating ROS, hereby producing DNA damage and cell death by apoptosis [195, 196]. This increasing of ROS seems to play an important ro.Ovarian tumors [173], among others [62, 174]. Another promising radiosensitizer is EGCG. This catechin has shown synergistic effects with radiation on radioresistant glioblastoma multiforme, multiple myeloma (IM-9), leukemia (K-562), and cancer cervix (HeLa) cells [125]. Moreover, a recent clinical trial showed that EGCG may improve the prognostic of breast cancer patients under radiotherapy [119]. Melatonin is one of the most studied antioxidants in recent years, both in in vitro and in vivo assays. As it was hypothesized by Vijayalaxmi et al. [175], melatonin may slow the saturation of repair enzymes. This fact would lead to repairing the damage caused by oxidative stress and also would allow the use of higher doses of radiation in the treatment, making melatonin an ideal protective agent during radiotherapy. Although, in most studies, melatonin has been used at very high doses (it is not toxic up to 250 mg/kg), itOxidative Medicine and Cellular Longevity was found that its administration at low doses in mice, over a period of time (e.g., 0.1 mg/kg/day for 15 days before receiving radiation), appeared to be quite effective, so that the suitable dose of melatonin for humans in radiotherapy treatments is an issue that has to be investigated in more depth [126] (Table 2(b)). As for chemotherapy, there are numerous agents that induce cell death by oxidative stress either directly, leading to the disruption of redox signaling and ROS scavenging, or indirectly by reducing intracellular levels of antioxidants and deactivating the cellular defense. Numerous articles have reported on many chemotherapeutic agents whose effects involve the induction of oxidative stress. Some of them are new molecules as Meroxest, a synthetic merosesquiterpene derivative of the trans-communic acid, plentiful in Cupressus sempervirens [176], or Jadomycin, which is synthesized by the bacteria Streptomyces venezuelae [177]. Other compounds are part of the current therapeutic repertoire, like oxaliplatin [178], bleomycin [179], gemcitabine [180, 181], cyclophosphamide [182], celecoxib [183], capecitabine [184, 185], bortezomib (a proteasome inhibitor, approved for the treatment of multiple myeloma) [186, 187], and arsenic trioxide (ATO). ATO, which is used in the treatment of acute promyelocytic leukemia (APL), can produce a loss of permeability of the outer mitochondrial membrane and impair the function of the respiratory chain, leading to an increase in superoxide anion [188?91]. However, many of the agents that induce oxidative stress have hardly any studies about the interaction between their antineoplastic activity and antioxidants. Then, we present the information about various antitumor drugs which have been selected according to their utility, therapeutic efficacy, and involvement in studies that were focused on the evaluation of the interaction with antioxidants during chemotherapy. Anthracyclines are antitumor antibiotics commonly used in chemotherapy. They have been linked to the generation of oxidative stress and increased ROS levels and could act as mediators of apoptosis by the activation of caspases 3 and 9 [192?94]. Doxorubicin (Adriamycin) is a widely anthracycline used in the treatment of various cancers, including solid breast and prostate tumors. It exerts its antitumor activity by inhibiting topoisomerase II and generating ROS, hereby producing DNA damage and cell death by apoptosis [195, 196]. This increasing of ROS seems to play an important ro.