N-bromotaurine surrogates for loss of antiproliferative response and enhances cisplatin efficacy in cancer cells with impaired glucocorticoid receptor

Stella Logotheti, Nikolas Khoury, Spiros A Vlahopoulos, Elena Skourti, Dimitra Papaevangeliou, Triantafyllos Liloglou, Vassilis Gorgoulis, Irina Budunova, Anthony M Kyriakopoulos, Vassilis Zoumpourlis

Research output: Contribution to journalArticle (journal)peer-review

10 Citations (Scopus)


Glucocorticoids (GCs) are frequently used in anticancer combination regimens; however, their continuous use adds selective pressure on cancer cells to develop GC-resistance via impairment of the glucocorticoid receptor (GR), therefore creating a need for GC-alternatives. Based on the drug repurposing approach and the commonalities between inflammation and neoplasia, drugs that are either in late-stage clinical trials and/or already marketed for GC-refractory inflammatory diseases could be evaluated as GC-substitutes in the context of cancer. Advantageously, unlike new molecular entities currently being de novo developed to restore GC-responsiveness of cancer cells, such drugs have documented safety and efficacy profile, which overall simplifies their introduction in clinical cancer trials. In this study, we estimated the potential of a well-established, multistage, cell line-based, mouse skin carcinogenesis model to be exploited as an initial screening tool for unveiling covert GC-substitutes. First, we categorized the cell lines of this model to GC-sensitive and GC-resistant, in correlation with their corresponding GR status, localization, and functionality. We found that GC-resistance starts in papilloma stages, due to a dysfunctional GR, which is overexpressed, DNA binding-competent, but transactivation-incompetent in papilloma, squamous, and spindle stages of the model. Then, aided by this tool, we evaluated the ability of N-bromotaurine, a naturally occurring, small-molecule, nonsteroid anti-inflammatory drug which is under consideration for use interchangeably/in replacement to GCs in skin inflammations, to restore antiproliferative response of GC-resistant cancer cells. Unlike GCs, N-bromotaurine inhibited cell-cycle progression in GC-resistant cancer cells and efficiently synergized with cisplatin, thus indicating a potential to be exploited instead of GCs against cancer.

Original languageEnglish
Pages (from-to)58-73.e2
JournalTranslational research : the journal of laboratory and clinical medicine
Publication statusPublished - 1 Jul 2016


  • Animals
  • Carcinogenesis/metabolism
  • Cell Cycle/drug effects
  • Cell Line, Tumor
  • Cell Proliferation/drug effects
  • Cisplatin/pharmacology
  • DNA/metabolism
  • Disease Models, Animal
  • Disease Progression
  • Drug Resistance, Neoplasm/drug effects
  • Glucocorticoids/pharmacology
  • Humans
  • Mice
  • Protein Binding/drug effects
  • Protein Transport/drug effects
  • Receptors, Glucocorticoid/metabolism
  • Response Elements/genetics
  • Skin Neoplasms/metabolism
  • Taurine/analogs & derivatives
  • Transcriptional Activation/drug effects


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