Relationship between Optical Redox Status and Reactive Oxygen Species in Cancer Cells

  • Allison Podsednik Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • Annemarie Jacob Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • Lin Z. Li Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • He N. Xu Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Keywords: Breast cancer; Intrinsic fluorescence; Flavoproteins; NADH; Optical redox imaging; Reactive oxygen species; Redox ratio

Abstract

Shifted NAD(H) redox status and enhanced reactive oxygen species (ROS) scavenging systems have been observed in cancers. However, how such redox shift is related to the ROS level in cancer cells is less clear. Based on collecting the intrinsic fluorescence of oxidized flavoproteins (Fp containing flavin adenine dinucleotide) and reduced nicotinamide adenine dinucleotide (NADH), optical redox imaging (ORI) provides a quantitative measure of the mitochondrial redox state by the optical redox ratio, Fp/(NADH+Fp), a surrogate marker of the NAD+-coupled redox state NAD+/NADH. Our study aims to explore the relationship between NAD(H) redox status and ROS by imaging NADH, Fp, and ROS levels using cultured breast cancer cell models. By manipulating either ROS levels via application of exogenous H2O2 or redox status via metabolic perturbation compounds, we found that: (1) oxidation of NAD(H) redox status correlates with ROS levels at lower H2O2 concentrations (up to ~700 µM), but not necessarily at higher concentrations; (2) an elevated ROS level diminishes NADH and reduces redox ratio plasticity; (3) either more oxidized or more reduced status can correlate to an increased ROS level; and (4) sometimes, a more oxidized status can correlate to a decreased ROS level depending on cell lines. These observations indicated that cellular NAD(H) redox state and ROS are intricately related but can also change separately. This study can benefit cancer research as both NAD(H) redox status and ROS have been implicated in cancer transformation and progression.

Published
2020-03-01
How to Cite
Podsednik, A., Jacob, A., Li, L. Z., & Xu, H. N. (2020). Relationship between Optical Redox Status and Reactive Oxygen Species in Cancer Cells. Reactive Oxygen Species, 9(26), 95–108. Retrieved from https://www.aimsci.com/ros/index.php/ros/article/view/261
Section
Original Research Articles