ROS Pleiotropy in Melanoma and Local Therapy with Physical Modalities

Abstract

Metabolic energy production naturally generates unwanted products such as reactive oxygen species (ROS), causing oxidative damage. Oxidative damage has been linked to several pathologies, including diabetes, premature aging, neurodegenerative diseases, and cancer. ROS were therefore originally anticipated as an imperative evil, a product of an imperfect system. More recently, however, the role of ROS in signaling and tumor treatment is increasingly acknowledged. This review addresses the main types, sources, and pathways of ROS in melanoma by linking their pleiotropic roles in antioxidant and oxidant regulation, hypoxia, metabolism, and cell death. In addition, the implications of ROS in various physical therapy modalities targeting melanoma, such as radiotherapy, electrochemotherapy, hyperthermia, photodynamic therapy, and medical gas plasma, are also discussed. By including ROS in the main picture of melanoma skin cancer and as an integral part of cancer therapies, a greater understanding of melanoma cell biology is presented, which ultimately may elucidate additional clues on targeting therapy resistance of this most deadly form of skin cancer.

Decoding the synergistic potential of MAZ‐51 and zingerone as therapy for melanoma treatment in alignment with sustainable development goals

“…However, during malignancy melanogenesis is a source of oxidative stress. Overexpressed ROS induces a melanocyte homeostatic imbalance thus compromising their viability and fostering their malignant transformation 124 . Taking into consideration the antioxidant activity of zingerone and acetyl zingerone and the role of ROS in promoting melanoma, we hypothesize that zingerone is a suitable therapeutic strategy to target oxidative stress and thus, inhibit melanoma genesis.…”

Diverse antitumor effects of ascorbic acid on cancer cells and the tumor microenvironment

“…Conversely, the balance of oxidative stress and antioxidant activity plays a crucial role in tumor development and progression. In melanoma, ROS are overproduced by mitochondria or NADPH oxidase, which promotes tumor development and progression through DNA damage-induced mutation of oncogenes and signal transduction via NF-κB ( 77 , 78 ). In addition, melanoma acquires metastatic potential due to enhanced production of antioxidant enzymes such as catalase and tolerance to oxidative stress ( 78 , 79 ).…”

“…In melanoma, ROS are overproduced by mitochondria or NADPH oxidase, which promotes tumor development and progression through DNA damage-induced mutation of oncogenes and signal transduction via NF-κB ( 77 , 78 ). In addition, melanoma acquires metastatic potential due to enhanced production of antioxidant enzymes such as catalase and tolerance to oxidative stress ( 78 , 79 ). Ascorbic acid has a dual impact on melanoma, with high concentrations triggering cell death and low amounts promoting tumor growth ( 80 ).…”

Involvement of Resveratrol against Brain Cancer: A Combination Strategy with a Pharmaceutical Approach

“…RES can disrupt a variety of faulty signaling pathways, allowing it to act as a functionally pleiotropic medication, targeting several targets in cancer cells while inflicting minimal harm to healthy cells. Some of the most significant cellular changes are accelerated cell cycle checkpoint transitions with abnormal cell proliferation, genome instability, abnormal response to signals or other stimulators of programmed cell death, uncontrolled neo angiogenesis, increased oxidative stress, overstimulation of growth regulatory hormones, and changes in host immune responses [ 134 ]. Anti-inflammatory, antioxidant, and immunomodulatory properties aid in the reduction of oxidative stress-induced damage (protein oxidation, DNA damage, and lipid peroxidation), as well as increasing immunological cancer surveillance.…”