Ouabain Effects on Human Anaplastic Thyroid Carcinoma 8505C Cells

SIMPLE SUMMARY: Anaplastic thyroid carcinoma is a rare and very aggressive thyroid carcinoma. Current conventional treatments for anaplastic thyroid carcinoma are not very effective, so there is an urgent need for new types of treatment for this disease. Some molecules known as cardiotonic steroids (e.g., ouabain), which were previously used for the treatment of patients with heart failure, appear to have anti-tumoral effects and cancer therapy potential. The aim of the present work was to analyze the effects of ouabain in human anaplastic thyroid carcinoma, using an anaplastic thyroid cell line (called 8505C) as the model. With this work, we hope to contribute to the study of the potential anti-tumoral roles of ouabain in the search for alternative anaplastic thyroid carcinoma treatments. ABSTRACT: Anaplastic thyroid carcinoma (ATC) is a rare, but aggressive, carcinoma derived from follicular cells. While conventional treatments may improve patients’ survival, the lethality remains high. Therefore, there is an urgent need for more effective ATC treatments. Cardiotonic steroids, such as ouabain, have been shown to have therapeutic potential in cancer treatment. Thus, we aimed to evaluate ouabain’s effects in human anaplastic thyroid cells. For this, 8505C cells were cultured in the presence or absence of ouabain. Viability, cell death, cell cycle, colony formation and migratory ability were evaluated in ouabain-treated and control 8505C cells. The expression of differentiation and epithelial-to-mesenchymal transition (EMT) markers, as well as IL-6, TGFb1 and their respective receptors were also quantified in these same cells. Our results showed that ouabain in vitro decreased the number of viable 8505C cells, possibly due to an inhibition of proliferation. A reduction in migration was also observed in ouabain-treated 8505C cells. In contrast, decreased mRNA levels of PAX8 and TTF1 differentiation markers and increased levels of the N-cadherin EMT marker, as well as IL-6 and TGFb1, were found in ouabain-treated 8505C cells. In short, ouabain may have anti-proliferative and anti-migratory effect on 8505C cells, but maintains an aggressive and undifferentiated profile.