Antioxidants in brain tumors: current therapeutic significance and future prospects

Abstract

Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. Antioxidants are hypothesized to inhibit cancer initiation by endorsing DNA repair and suppressing cancer progression by creating an energy crisis for preneoplastic cells, resulting in antiproliferative effects. These effects are referred to as chemopreventive effects mediated by an antioxidant mechanism. In addition, antioxidants minimize chemotherapy-induced nonspecific organ toxicity and prolong survival. Antioxidants also support the prooxidant chemistry that demonstrate chemotherapeutic potential, particularly at high or pharmacological doses and trigger OS by promoting free radical production, which is essential for activating cell death pathways. A growing body of evidence also revealed the roles of exogenous antioxidants as adjuvants and their ability to reverse chemoresistance. In this review, we explain the influences of different exogenous and endogenous antioxidants on brain cancers with reference to their chemopreventive and chemotherapeutic roles. The role of antioxidants on metabolic reprogramming and their influence on downstream signaling events induced by tumor suppressor gene mutations are critically discussed. Finally, the review hypothesized that both pro- and antioxidant roles are involved in the anticancer mechanisms of the antioxidant molecules by killing neoplastic cells and inhibiting tumor recurrence followed by conventional cancer treatments. The requirements of pro- and antioxidant effects of exogenous antioxidants in brain tumor treatment under different conditions are critically discussed along with the reasons behind the conflicting outcomes in different reports. Finally, we also mention the influencing factors that regulate the pharmacology of the exogenous antioxidants in brain cancer treatment. In conclusion, to achieve consistent clinical outcomes with antioxidant treatments in brain cancers, rigorous mechanistic studies are required with respect to the types, forms, and stages of brain tumors. The concomitant treatment regimens also need adequate consideration.

Hypericum alpestre extract exhibits in vitro and in vivo anticancer properties by regulating the cellular antioxidant system and metabolic pathway of L‐arginine

“…The latter was accompanied by a decrease in the concentration of MDA in the blood and tumors, which also confirmed the antioxidant protective effect of the extract. From the published literature, antioxidant protection leads to anti‐inflammatory, antiproliferative, antimetastatic, and antiangiogenic effects 95 . The above‐mentioned processes were studied by evaluating the changes in the activity of arginase, the quantity of polyamines, NO, and IL‐2, and breast histological analysis.…”

“…From the published literature, antioxidant protection leads to antiinflammatory, antiproliferative, antimetastatic, and antiangiogenic effects. 95 The above-mentioned processes were studied by evaluat- The activity of arginase and NOS enzymes may be accompanied by an increase in the activity of COX-2, which is a key process in inflammation. 97 Further studies will be needed to determine the role of HA in immune responses in the settings of breast cancer.…”

Metabolomic profiling of wild rooibos (Aspalathus linearis) ecotypes and their antioxidant-derived phytopharmaceutical potential

“…It is known that plants commonly produce antioxidants, however, the degree of antioxidant activity may be higher when species-specific metabolites with specialised antioxidant activity are present (Zonyane et al, 2020 ). The antioxidant activity of natural antioxidant substances is uncertain and condition dependent, therefore it is important to perform both in vitro and in vivo analysis before making claims with regards to potentially therapeutic antioxidant substances (Gupta et al, 2020 ; Qi et al, 2022 ). In this particular study, an in vitro assay was thus conducted.…”

CAR T cells: engineered immune cells to treat brain cancers and beyond

“…The classical therapeutic scheme of brain cancer includes surgical resection followed by chemotherapy and/or radiation therapy. However, a growing body of evidence revealed that the chances of relapse are very high for malignant brain tumors [ 8 , 9 ].…”