Subject:
|
Molecular Biology Radboudumc 18: Healthcare improvement science RIHS: Radboud Institute for Health Sciences Radboudumc 19: Nanomedicine RIMLS: Radboud Institute for Molecular Life Sciences Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences Radboudumc 6: Metabolic Disorders RIMLS: Radboud Institute for Molecular Life Sciences Radboudumc 9: Rare cancers RIMLS: Radboud Institute for Molecular Life Sciences |
Organization:
|
Pathology Biochemistry (UMC) Medical Imaging Pharmacology-Toxicology Molecular Biology Internal Medicine |
Journal title:
|
Molecular Cancer Therapeutics
|
Abstract:
|
Up to 20%-30% of patients with metastatic non-medullary thyroid cancer have persistent or recurrent disease resulting from tumor dedifferentiation. Tumor redifferentiation to restore sensitivity to radioactive iodide (RAI) therapy is considered a promising strategy to overcome RAI resistance. Autophagy has emerged as an important mechanism in cancer dedifferentiation. Here, we demonstrate the therapeutic potential of autophagy activators for redifferentiation of thyroid cancer cell lines. Five autophagy-activating compounds, all known as digitalis-like compounds, restored hNIS expression and iodide uptake in thyroid cancer cell lines. Upregulation of hNIS was mediated by intracellular Ca2+ and FOS activation. Cell proliferation was inhibited by downregulating AKT1 and by induction of autophagy and p21-dependent cell-cycle arrest. Digitalis-like compounds, also designated as cardiac glycosides for their well-characterized beneficial effects in the treatment of heart disease, could therefore represent a promising repositioned treatment modality for patients with RAI-refractory thyroid carcinoma. Mol Cancer Ther; 16(1); 169-81. (c)2016 AACR.
|