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  • Expression of the thioredoxin system in an in vivo-like cancer cell environment upon auranofin treatment

    Author(s)
    Bhatia, Maneet
    Lovitt, Carrie J
    Raninga, Prahlad V
    Avery, Vicky M
    Di Trapani, Giovanna
    Tonissen, Kathryn F
    Griffith University Author(s)
    Di Trapani, Jenny
    Tonissen, Kathryn F.
    Avery, Vicky M.
    Year published
    2016
    Metadata
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    Abstract
    As essential elements of the tumor microenvironment, the variable oxygenation state of the tumor tissue, the extracellular matrix (ECM) and different cell types are important determinants of carcinogenesis. These elements may also influence how tumor cells respond to therapeutic treatments. In the present study, we assessed the anti-cancer activity of auranofin and its effect on the thioredoxin (Trx) system under conditions that closely resemble the in vivo tumor microenvironment with respect to the oxygen levels and tissue architecture. We utilised an oxygen scheme involving growth of cancer cells under normoxia (20%) and ...
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    As essential elements of the tumor microenvironment, the variable oxygenation state of the tumor tissue, the extracellular matrix (ECM) and different cell types are important determinants of carcinogenesis. These elements may also influence how tumor cells respond to therapeutic treatments. In the present study, we assessed the anti-cancer activity of auranofin and its effect on the thioredoxin (Trx) system under conditions that closely resemble the in vivo tumor microenvironment with respect to the oxygen levels and tissue architecture. We utilised an oxygen scheme involving growth of cancer cells under normoxia (20%) and hypoxia (0.1%). We also preconditioned cells with intermittent hypoxia (IH) prior to a prolonged hypoxic incubation. This oxygen scheme did not affect the cytotoxicity of auranofin; however, IH preconditioned cells were less sensitive towards the inhibition of thioredoxin reductase (TrxR) specific activity upon treatment with auranofin. IH preconditioning also upregulated Trx protein levels in auranofin treated cells. We also compared the activity of auranofin against cancer cells cultured in 2D monolayer and 3D spheroid-based culture models. Auranofin was less potent against cells grown under a more in vivo-like 3D environment. The results presented in this paper implicate the importance of the tumor oxygen environment and tissue architecture in influencing the response of cancer cells towards auranofin.
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    Journal Title
    European Journal of Cell Biology
    Volume
    95
    Issue
    10
    DOI
    https://doi.org/10.1016/j.ejcb.2016.08.003
    Subject
    Biochemistry and cell biology
    Biochemistry and cell biology not elsewhere classified
    Plant biology
    Publication URI
    http://hdl.handle.net/10072/100532
    Collection
    • Journal articles

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