Antioxidative Stress: Inhibiting Reactive Oxygen Species Production as a Cause of Radioresistance and Chemoresistance

Abstract

Radiotherapy and chemotherapy are the most effective nonsurgical treatments for cancer treatment. They usually induce regulated cell death by increasing the level of reactive oxygen species (ROS) in tumour cells. However, as intracellular ROS concentration increases, many antioxidant pathways are concurrently upregulated by cancer cells to inhibit ROS production, ultimately leading to drug resistance. Understanding the mechanism of antioxidant stress in tumour cells provides a new research direction for overcoming therapeutic resistance. In this review, we address (1) how radiotherapy and chemotherapy kill tumour cells by increasing the level of ROS, (2) the mechanism by which ROS activate antioxidant pathways and the subsequent cellular mitigation of ROS in radiotherapy and chemotherapy treatments, and (3) the potential research direction for targeted treatment to overcome therapeutic resistance.

Dietary Phytochemicals Targeting Nrf2 to Enhance the Radiosensitivity of Cancer

“…Under physiological circumstance, intracellular ROS is kept at a relatively low level and is precisely controlled by the scavengers, such as glutathione, thioredoxin, peroxidase, and catalase [ 55 ]. However, the increased ROS scavenging substances levels or the enhancements of antioxidant defense systems might contribute to radioresistance in cancer cells [ 56 , 57 ]. Radioresistance is the process by which the tumor cells or tissues adapt to RT and develop resistance to it [ 58 ].…”

Targeting Mitochondrial Metabolism to Reverse Radioresistance: An Alternative to Glucose Metabolism

“…Under normal physiological conditions, cells tend to maintain redox homeostasis, that is, the balance between the production of free radicals and reactive metabolites (oxidants, ROS, or reactive nitrogen species) and their elimination through protective mechanisms (antioxidant systems) [ 37 ]. When the balance between ROS and antioxidants is disrupted, the body is in a state of oxidative stress, resulting in damage to important biomolecules and cells with potential effects on the entire organism [ 38 ]. It is worth noting that oxidative stress is generally present in tumor cells, and data show that the concentration of ROS is usually 10 times higher than that in normal cells, which may further lead to DNA mutation, genomic instability, and tumor cell proliferation [ 39 ].…”

Sulforaphane Impact on Reactive Oxygen Species (ROS) in Bladder Carcinoma

“…These findings coincide with observations regarding radiotherapy and chemotherapy. Both strategies induce oxidative stress and ROS-mediated cell damage in cancer cells by increasing ROS above a critical threshold, necessary to initiate apoptosis [ 28 , 29 , 30 ]. Thus, though an intracellular increase of ROS may force tumor growth and progression, excessive ROS levels may become toxic to the cells [ 31 ].…”

“…The interaction between PI3K/Akt signaling and ROS, which accumulates in cancer cells, has been the subject of several investigations. In fact, ROS-dependent activation of PI3K-AKT has been observed in many cancer types [ 30 ]. Akt activation is initiated by the oxidization and inactivation of the functional antagonist phosphatase and tensin homologue (PTEN) [ 89 ].…”