Is redox signaling a feasible target for overcoming multidrug resistance in cancer chemotherapy?

Manuela Polimeni,Elena Gazzano

doi:10.3389/fphar.2014.00286

Abstract

Under physiological conditions, a balance between oxidants and antioxidants exists. Reactive oxygen species (ROS), are continuously generated by aerobic cells and eliminated through scavenging systems to maintain redox homeostasis. The two main sources of ROS are mitochondria and the NADPH oxidases family, but ROS are produced also by the cytochrome P450 system, xanthine oxidase and nitric oxide synthase (Holmstrom and Finkel, 2014). Because of ROS reactivity toward lipids, proteins and DNA, spatial and temporal regulatory strategies exist to regulate their intracellular levels. Excessive ROS levels are controlled by specific intracellular enzymes, such as superoxide dismutase (SOD), glutathione peroxidase, catalase, thioredoxin reductase, and glutathione S-transferase (Glasauer and Chandel, 2014).

Highlights

Under physiological conditions, a balance between oxidants and antioxidants exists
Cancer cells are dependent on maintaining high enough Reactive oxygen species (ROS) levels and an altered redox environment that allow for protumorigenic cell signaling without inducing cell death (Glasauer and Chandel, 2014)
Both carcinogenesis and multidrug resistance (MDR) are frequently associated with an increased oxidative stress and activation of redox metabolism: this could affect the efficacy of cancer treatments by multiple mechanisms, including apoptosis, angiogenesis, metastasis, inflammatory reaction, and chemosensitivity (Morrow et al, 2006; Kuo, 2009)

Summary

Introduction

A balance between oxidants and antioxidants exists. Reactive oxygen species (ROS), are continuously generated by aerobic cells and eliminated through scavenging systems to maintain redox homeostasis. Cells aim to maintain a redox homeostasis: low levels of ROS, which are locally produced, can be potent mitogens and are required for various biological processes such as cell survival, growth and proliferation, angiogenesis, gene expression (Finkel, 2012). Both carcinogenesis and MDR are frequently associated with an increased oxidative stress and activation of redox metabolism: this could affect the efficacy of cancer treatments by multiple mechanisms, including apoptosis, angiogenesis, metastasis, inflammatory reaction, and chemosensitivity (Morrow et al, 2006; Kuo, 2009).

Results

Conclusion