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@ARTICLE{Kratz:361506,
      author       = {Kratz, Katja and Förster, Henrieke and Vogel, Kira and
                      Durante, Marco and Jakob, Burkhard},
      title        = {2-{D}eoxy-{D}-{G}lucose and {ES}-936 sensitize cancer- but
                      not normal cells to both low- and high {LET} irradiation},
      journal      = {Frontiers in oncology},
      volume       = {15},
      issn         = {2234-943X},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {GSI-2025-00970},
      pages        = {1633299},
      year         = {2025},
      note         = {This is an open-access article distributed under the terms
                      of the Creative Commons Attribution License (CC BY).},
      abstract     = {Metabolic differences of normal- and cancer cells represent
                      an important target for the development of novel cancer
                      treatment strategies. Given that radiotherapy constitutes
                      one of the primary treatment modalities for solid cancers,
                      the targeting of cancer cell metabolism to enhance their
                      sensitivity to irradiation emerges as a promising approach.
                      The utilization of glycolysis even under aerobic conditions
                      in cancer cells presents a unique target to deprive cancer
                      cells of energy and metabolites required not only for their
                      rapid cell growth but also for the repair of irradiation
                      induced DNA damage. Furthermore, cancer cells have been
                      observed to exhibit elevated levels of reactive oxygen
                      species and potentially react more sensitively to an induced
                      disturbance of the redox balance, especially after
                      irradiation mediated oxidative stress. Overall, interference
                      with aerobic glycolysis and the oxidative stress response
                      could potentiate the anti-proliferative and cytotoxic
                      effects of cancer cell irradiation, while sparing normal
                      cells.To analyze the effect of inhibitors targeting the
                      cellular metabolism and redox balance, normal fibroblast-
                      and cancer cell lines were characterized using a Seahorse
                      XFp metabolic analyzer, followed by Sulforhodamin B
                      proliferation assays and flow cytometry based cell cycle
                      analysis. Furthermore, NADP+/NADPH-, NAD(P)H- and ROS levels
                      were determined using bioluminescent assays, Fluorescence
                      Lifetime Imaging Microscopy (FLIM) and fluorescent
                      microscopy. Radiosensitization of cell lines was assessed
                      through clonogenic survival assays and analyses of
                      DNA-repair efficiency via fluorescence microscopy.The
                      present study demonstrates that the glycolytic inhibitor
                      2-deoxy-D-glucose and the NAD(P)H:quinone oxidoreductase
                      inhibitor ES-936 can render cancer cells more sensitive to
                      X-rays and densely ionizing radiation (high-linear energy
                      transfer (LET) irradiation) like alpha-particles or heavy
                      ions but do not affect normal fibroblasts. While
                      inhibitor-treated and low-LET (X-ray) irradiated cancer
                      cells exhibited a decreased clonal survival, an additional
                      DNA repair defect was observed after high-LET
                      irradiation.Our results imply that distinct mechanisms
                      influence the clonal survival and DNA repair of irradiated,
                      inhibitor-treated cancer cells in dependence of the LET. The
                      findings of this study suggest that the combination of
                      inhibitors targeting glycolysis and the redox balance may
                      represent a promising strategy to enhance the sensitivity of
                      cancer cells to both photon- and charged particle therapy.},
      keywords     = {2-deoxy-D-glucose (Other) / DNA-repair (Other) / cancer
                      (Other) / carbon-ions (Other) / glycolysis (Other) /
                      high-LET (Other) / metabolism (Other) / radiotherapy
                      (Other)},
      cin          = {BIO},
      ddc          = {610},
      cid          = {I:(DE-Ds200)BIO-20160831OR354},
      pnm          = {633 - Life Sciences – Building Blocks of Life: Structure
                      and Function (POF4-633) / 02NUK054A - Verbundprojekt
                      VERCHROMT II: Erkennung, Verarbeitung und biologische
                      Konsequenzen von Chromatinschäden nach Teilchenbestrahlung
                      II, Teilprojekt A (BMBF-02NUK054A) / FAIR Phase-0 - FAIR
                      Phase-0 Research Program (GSI-FAIR-Phase-0) /
                      SUC-GSI-Darmstadt - Strategic university cooperation GSI-TU
                      Darmstadt (SUC-GSI-DA)},
      pid          = {G:(DE-HGF)POF4-633 / G:(DE-Ds200)BMBF-02NUK054A /
                      G:(Ds200)GSI-FAIR-Phase-0 / G:(DE-Ds200)SUC-GSI-DA},
      experiment   = {$EXP:(DE-Ds200)UBio08_Jakob-20221208$},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {40900796},
      UT           = {WOS:001563580900001},
      doi          = {10.3389/fonc.2025.1633299},
      url          = {https://repository.gsi.de/record/361506},
}