Faculty Collaboration Database

Teaching the basics of reactive oxygen species and their relevance to cancer biology: Mitochondrial reactive oxygen species detection, redox signaling, and targeted therapies. Redox Biol 2018 May;15:347-362

Date

01/08/2018

Pubmed ID

29306792

Pubmed Central ID

PMC5756055

DOI

10.1016/j.redox.2017.12.012

Scopus ID

2-s2.0-85039930921 (requires institutional sign-in at Scopus site)   161 Citations

Abstract

Reactive oxygen species (ROS) have been implicated in tumorigenesis (tumor initiation, tumor progression, and metastasis). Of the many cellular sources of ROS generation, the mitochondria and the NADPH oxidase family of enzymes are possibly the most prevalent intracellular sources. In this article, we discuss the methodologies to detect mitochondria-derived superoxide and hydrogen peroxide using conventional probes as well as newly developed assays and probes, and the necessity of characterizing the diagnostic marker products with HPLC and LC-MS in order to rigorously identify the oxidizing species. The redox signaling roles of mitochondrial ROS, mitochondrial thiol peroxidases, and transcription factors in response to mitochondria-targeted drugs are highlighted. ROS generation and ROS detoxification in drug-resistant cancer cells and the relationship to metabolic reprogramming are discussed. Understanding the subtle role of ROS in redox signaling and in tumor proliferation, progression, and metastasis as well as the molecular and cellular mechanisms (e.g., autophagy) could help in the development of combination therapies. The paradoxical aspects of antioxidants in cancer treatment are highlighted in relation to the ROS mechanisms in normal and cancer cells. Finally, the potential uses of newly synthesized exomarker probes for in vivo superoxide and hydrogen peroxide detection and the low-temperature electron paramagnetic resonance technique for monitoring oxidant production in tumor tissues are discussed.

Author List

Kalyanaraman B, Cheng G, Hardy M, Ouari O, Bennett B, Zielonka J

Authors

Brian Bennett D.Phil. Professor and Chair in the Physics department at Marquette University
Gang Cheng PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin
Micael Joel Hardy PhD Visiting Assistant Professor in the Biophysics department at Medical College of Wisconsin
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin
Jacek M. Zielonka PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Humans
Hydrogen Peroxide
Mitochondria
Molecular Targeted Therapy
NADPH Oxidases
Neoplasms
Oxidation-Reduction
Reactive Oxygen Species
Superoxides