Increased formation of reactive oxygen species during tumor growth: Ex vivo low-temperature EPR and in vivo bioluminescence analyses

Gang Cheng, Jing Pan, Radoslaw Podsiadly, Jacek Zielonka, Alexander M. Garces, Luiz Gabriel Dias Duarte Machado, Brian Bennett, Donna McAllister, Michael B. Dwinell, Ming You, Balaraman Kalyanaraman

    Research output: Contribution to journalArticlepeer-review

    16 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)167-174
    Number of pages8
    JournalFree Radical Biology and Medicine
    Volume147
    DOIs
    StatePublished - Feb 1 2020

    Keywords

    • Bioluminescence
    • EPR
    • Mitochondria
    • Oxidants
    • Tumor growth

    ASJC Scopus subject areas

    • Biochemistry
    • Physiology (medical)

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