ROS in cancer therapy: the bright side of the moon

Abstract

Reactive oxygen species (ROS) constitute a group of highly reactive molecules that have evolved as regulators of important signaling pathways. It is now well accepted that moderate levels of ROS are required for several cellular functions, including gene expression. The production of ROS is elevated in tumor cells as a consequence of increased metabolic rate, gene mutation and relative hypoxia, and excess ROS are quenched by increased antioxidant enzymatic and nonenzymatic pathways in the same cells. Moderate increases of ROS contribute to several pathologic conditions, among which are tumor promotion and progression, as they are involved in different signaling pathways and induce DNA mutation. However, ROS are also able to trigger programmed cell death (PCD). Our review will emphasize the molecular mechanisms useful for the development of therapeutic strategies that are based on modulating ROS levels to treat cancer. Specifically, we will report on the growing data that highlight the role of ROS generated by different metabolic pathways as Trojan horses to eliminate cancer cells.

Screening of Health-Associated Oral Bacteria for Anticancer Properties in vitro

“…H 2 O 2 induces oxidative stress in mammalian cells which signals the activation of several cellular pathways including of pro-inflammatory cytokine production and cell death or apoptosis (Pelaia et al, 2004 ; Valko et al, 2007 ; Forman et al, 2010 ; Vilema-Enriquez et al, 2016 ; Park, 2018 ; Aggarwal et al, 2019 ). H 2 O 2 acts as double-edged sword; while it is shown to be a potent carcinogen in normal cells (Lisanti et al, 2011 ), localized production of H 2 O 2 has been used in hyperoxygenation therapy for cancer treatment (Liu and Wang, 2015 ; Vilema-Enriquez et al, 2016 ; Mast and Kuppusamy, 2018 ; Perillo et al, 2020 ). Studies have also shown that cancer cells are more sensitive to H 2 O 2 than normal cells (Aykin-Burns et al, 2009 ) which has led to increased interest in exploring its therapeutic potential for cancer treatment including oral cancer.…”

Extracellular Neuroglobin as a Stress-Induced Factor Activating Pre-Adaptation Mechanisms against Oxidative Stress and Chemotherapy-Induced Cell Death in Breast Cancer

“…For example, oxidative stress induces the release of intracellular proteins through non-classical mechanisms [ 48 , 49 ] and it promotes exosome secretion from cancer cells [ 50 ]. Oxidative stress is a common feature of high proliferating cancer tissue and moderate levels of ROS and in particular, H 2 O 2 , directly impact on different aspects of cancer phenotype affecting signal transduction pathways [ 51 , 52 ]. Indeed, during cancer transformation low/moderate levels of ROS has been demonstrated to act as signaling molecules activating MAPK/ERK1/2 and AKT pathways and contributing to cancer cell proliferation, survival, and motility [ 51 ].…”

“…Indeed, during cancer transformation low/moderate levels of ROS has been demonstrated to act as signaling molecules activating MAPK/ERK1/2 and AKT pathways and contributing to cancer cell proliferation, survival, and motility [ 51 ]. On the opposite, a stronger and toxic oxidative stress would be deleterious also for cancer cells triggering, preferentially, a pro-apoptotic p38/MAPK pathway [ 52 ]. Of note, among the different signaling pathways affected by oxidative stress, evidence indicates that AKT signaling also contributes to the regulation of protein secretion through the non-classical pathway as reported for FGF-1 [ 53 ].…”

Low Dose Astaxanthin Treatments Trigger the Hormesis of Human Astroglioma Cells by Up-Regulating the Cyclin-Dependent Kinase and Down-Regulated the Tumor Suppressor Protein P53

“…Indeed, a study in esophageal squamous cell carcinoma suggested that an increase in the SOD-2 levels resulted in resistance to cisplatin in the related cells [ 48 ]. ROS control is considered to be an effective cancer treatment method [ 49 ]. However, our data suggest that cellular uptake should be carefully considered, as it might have outcomes opposite to those intended.…”