n-bromotaurine and Disease-Models--Animal

For one century, taurine is considered as an end product of sulfur metabolism. In this review, we discuss the beneficial effect of taurine, its haloamines and taurine upregulated gene 1 (TUG1) long non‑coding RNA (lncRNA) in both cancer and inflammation. We outline how taurine or its haloamines (N‑Bromotaurine or N‑Chlorotaurine) can induce robust and efficient responses against inflammatory diseases, providing insight into their molecular mechanisms. We also provide information about the use of taurine as a therapeutic approach to cancer. Taurine can be combined with other chemotherapeutic drugs, not only mediating durable responses in various malignancies, but also circumventing the limitations met from chemotherapeutic drugs, thus improving the therapeutic outcome. Interestingly, the lncRNA TUG1 is regarded as a promising therapeutic approach, which can overcome acquired resistance of cancer cells to selected strategies. In this regard, we can translate basic knowledge about taurine and its TUG1 lncRNA into potential therapeutic options directed against specific oncogenic signaling targets, thereby bridging the gap between bench and bedside.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Cell Proliferation; Disease Models, Animal; Disease Progression; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Neoplasms; Prognosis; RNA, Long Noncoding; Taurine

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.

Topics: Animals; Carcinogenesis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cisplatin; Disease Models, Animal; Disease Progression; DNA; Drug Resistance, Neoplasm; Glucocorticoids; Humans; Mice; Protein Binding; Protein Transport; Receptors, Glucocorticoid; Response Elements; Skin Neoplasms; Taurine; Transcriptional Activation