Patients with anaplastic thyroid carcinoma (ATC) have a poor prognosis, potentially caused by the presence of CD133+ cancer stem cell (CSC) subsets within ATC that are resistant to current modes of chemotherapy. In this study, Tseng et al. evaluated the role of signal transducer and activator of transcription 3 (STAT3) in the maintenance of stem cell-like properties of CD133+ ATC cells using cucurbitacin I, an inhibitor of STAT3 (p-STAT3) tyrosine phosphorylation. Cucurbitacin I diminished ATC-CD133+ cell CSC-like abilities, inhibited their “stemness” gene signature, and facilitated their differentiation into ATC-CD133− cells. Cucurbitacin I also up-regulated expression of thyroid-specific genes, including sodium iodide symporter, thyroperoxidase, and thyroglobulin, and it significantly enhanced sodium/iodide symporter-mediated radioiodine uptake. Cucurbitacin I increased sensitivity of ATC-CD133+ cells to radiation and chemotherapy through apoptosis. In vivo, cucurbitacin I, when combined with radiochemotherapy, significantly suppressed ATC-CD133+ xenograft growth and survival. These studies suggest that cucurbitacin I can potently attenuate the malignancy of ATC-CD133+ cells, and that the STAT3 pathway plays a key role in mediating CSC properties of ATC-CD133+ cells. Therefore, targeting STAT3 with cucurbitacin I may present a potential clinical benefit for thyroid cancer and overall for CSC treatment in the future.
See article at J Pharmacol Exp Ther 2012, 341:410–423.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics