Harnessing altered oxidative metabolism in cancer by augmented prooxidant therapy. (28th February 2020)

• Record Type: Journal Article
• Authors: Firczuk, Malgorzata; Bajor, Malgorzata; Graczyk-Jarzynka, Agnieszka; Fidyt, Klaudyna; Goral, Agnieszka; Zagozdzon, Radoslaw
• Is Part Of: Cancer letters. Volume 471(2020)
• Page Start: 1
• Page End: 11
• Publication Date: 2020-02-28
• Subjects: Reactive oxygen species -- Peroxiredoxin -- Thioredoxin -- Glutathione -- Ascorbate -- Polyphenols -- Cell death; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2019.11.037
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Deregulated metabolism of oxygen with increased generation of reactive oxygen species (ROS) is characteristic for a majority of cancers. The elevated ROS levels are in part responsible for further progression of cancer, but when produced in large excess, they endanger the viability of the cancer cells. To protect themselves from ROS-mediated toxicity, many types of cancers enhance the intrinsic antioxidant defenses, which make them dependent on the efficacy of a given ROS-detoxifying system. This poses an attractive target for anticancer therapy by two main approaches: the use of ROS-generating agents (i.e., prooxidants) or by inhibition of a chosen antioxidant system. However, the clinical efficacy of either of these approaches used alone is modest at best. The solution may rely on combining these strategies into an advanced prooxidant therapy (APoT) in order to produce a synergistic and cancer-specific effect. Indeed, such strategies have proven efficient in preclinical models, e.g., in B cell malignancies and breast cancer. Following promising experimental reports on APoT, this approach needs to be further extensively tested in order to become a potential alternative or an enhancement for classical chemotherapy. Highlights: Elevated concentrations of reactive oxygen species (ROS) are characteristic for cellular metabolism in advanced cancers. Cancer cell survival is dependent on the effective removal of exaggerated amounts of ROS by antioxidant mechanisms. Prooxidants modestly induce cancer cell death by production of ROS, but cancer cells adapt by increasing antioxidants. Combination of prooxidants with inhibitors of antioxidant defenses produce synergistic effects leading to cancer cells death.