Butyrate alters the expression and activity of cell cycle components in anaplastic thyroid carcinoma cells

Anaplastic thyroid carcinoma (ATC) is the most malignant and aggressive for m of thyroid cancer. Most patients die within months of diagnosis, primaril y due to the absence of effective chemotherapeutic strategies. Identifying alternative therapies is necessary to increase long-term survival. But)irat e elicits a number of responses from cancer cells both in vitro and in vivo including growth repression, cell cycle arrest, differentiation, and apopt osis. Even though many types of cancer cells have been studied, little is k nown of the response of ATC cells to this drug. In this study, we report th at butyrate induces differential cell cycle arrest (arrest in G(1) and G(2) /M phases) in an ATC cell line that correlates with changes in the expressi on, phosphorylation, and activity of key components of the cell cycle machi nery. Exposure to butyrate increases the expression of the cyclin-dependent kinase inhibitors, p21/Cip1 and p27/Kip1, decreases the expression of cycl in A and cyclin B, inhibits the phosphorylation of the retinoblastoma prote in (pRb), and decreases the activity of cdk1 and cdk2-associated kinases. T hese results suggest that butyrate may be useful in the clinical treatment of ATC.