TY - JOUR
T1 - Increased formation of reactive oxygen species during tumor growth
T2 - Ex vivo low-temperature EPR and in vivo bioluminescence analyses
AU - Cheng, Gang
AU - Pan, Jing
AU - Podsiadly, Radoslaw
AU - Zielonka, Jacek
AU - Garces, Alexander M.
AU - Dias Duarte Machado, Luiz Gabriel
AU - Bennett, Brian
AU - McAllister, Donna
AU - Dwinell, Michael B.
AU - You, Ming
AU - Kalyanaraman, Balaraman
N1 - Funding Information:
This work was supported by the Medical College of Wisconsin Cancer Center. Low-temperature EPR was supported in part by NSF Major Research Instrumentation award CHE-1532168 to BB and by the National Cancer Institute of the National Institutes of Health under Award Numbers U01 CA178960 (to MD and BK) and R01 CA208648 (to MY and BK). R.P. was supported by Polish National Science Centre within the SONATA BIS program (Grant Number 2016/22/E/ST4/00549). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
This work was supported by the Medical College of Wisconsin Cancer Center . Low-temperature EPR was supported in part by NSF Major Research Instrumentation award CHE-1532168 to BB and by the National Cancer Institute of the National Institutes of Health under Award Numbers U01 CA178960 (to MD and BK) and R01 CA208648 (to MY and BK) . R.P. was supported by Polish National Science Centre within the SONATA BIS program (Grant Number 2016/22/E/ST4/00549 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Appendix A
Publisher Copyright:
© 2019 Elsevier Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Previous studies have shown that reactive oxygen species (ROS) such as superoxide or hydrogen peroxide generated at low levels can exert a tumor-promoting role via a redox-signaling mechanism. Reports also suggest that both tumorigenesis and tumor growth are associated with enhanced ROS formation. However, whether ROS levels or ROS-derived oxidative marker levels increase during tumor growth remains unknown. In this study, in vivo bioluminescence imaging with a boronate-based pro-luciferin probe was used to assess ROS formation. Additionally, probe-free cryogenic electron paramagnetic resonance was used to quantify a characteristic aconitase [3Fe4S]+ center that arises in the tumor tissue of mouse xenografts from the reaction of the native [4Fe4S]2+ cluster with superoxide. Results indicated that tumor growth is accompanied by increased ROS formation, and revealed differences in oxidant formation in the inner and outer sections of tumor tissue, respectively, demonstrating redox heterogeneity. Studies using luciferin and pro-luciferin probes enabled the assessment of tumor size, ROS formation, and bioenergetic status (e.g., ATP) in luciferase-transfected mice tumor xenografts. Probe-free ex vivo low-temperature electron paramagnetic resonance can also be translated to clinical studies.
AB - Previous studies have shown that reactive oxygen species (ROS) such as superoxide or hydrogen peroxide generated at low levels can exert a tumor-promoting role via a redox-signaling mechanism. Reports also suggest that both tumorigenesis and tumor growth are associated with enhanced ROS formation. However, whether ROS levels or ROS-derived oxidative marker levels increase during tumor growth remains unknown. In this study, in vivo bioluminescence imaging with a boronate-based pro-luciferin probe was used to assess ROS formation. Additionally, probe-free cryogenic electron paramagnetic resonance was used to quantify a characteristic aconitase [3Fe4S]+ center that arises in the tumor tissue of mouse xenografts from the reaction of the native [4Fe4S]2+ cluster with superoxide. Results indicated that tumor growth is accompanied by increased ROS formation, and revealed differences in oxidant formation in the inner and outer sections of tumor tissue, respectively, demonstrating redox heterogeneity. Studies using luciferin and pro-luciferin probes enabled the assessment of tumor size, ROS formation, and bioenergetic status (e.g., ATP) in luciferase-transfected mice tumor xenografts. Probe-free ex vivo low-temperature electron paramagnetic resonance can also be translated to clinical studies.
KW - Bioluminescence
KW - EPR
KW - Mitochondria
KW - Oxidants
KW - Tumor growth
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U2 - 10.1016/j.freeradbiomed.2019.12.020
DO - 10.1016/j.freeradbiomed.2019.12.020
M3 - Article
C2 - 31874251
AN - SCOPUS:85076857582
VL - 147
SP - 167
EP - 174
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -