Abstract
Anaplastic thyroid carcinoma (ATC) is the most malignant and aggressive form of thyroid cancer. Most patients die within months of diagnosis, primarily due to the absence of effective chemotherapeutic strategies. Identifying alternative therapies is necessary to increase long-term survival. Butyrate elicits a number of responses from cancer cells both in vitro and in vivo including growth repression, cell cycle arrest, differentiation, and apoptosis. Even though many types of cancer cells have been studied, little is known of the response of ATC cells to this drug. In this study, we report that butyrate induces differential cell cycle arrest (arrest in G1 and G2/M phases) in an ATC cell line that correlates with changes in the expression, phosphorylation, and activity of key components of the cell cycle machinery. Exposure to butyrate increases the expression of the cyclin-dependent kinase inhibitors, p21/Cip1 and p27/Kip1, decreases the expression of cyclin A and cyclin B, inhibits the phosphorylation of the retinoblastoma protein (pRb), and decreases the activity of cdk1 and cdk2-associated kinases. These results suggest that butyrate may be useful in the clinical treatment of ATC.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Butyrates / pharmacology*
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CDC2 Protein Kinase / antagonists & inhibitors
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CDC2-CDC28 Kinases*
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Carcinoma / pathology*
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Cell Cycle / drug effects*
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Cell Cycle Proteins*
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Cyclin A / genetics
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Cyclin B / genetics
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclin-Dependent Kinases / antagonists & inhibitors
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Cyclins / genetics
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Enzyme Inhibitors / pharmacology
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G1 Phase / drug effects
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G2 Phase / drug effects
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Gene Expression / drug effects*
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Humans
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Microtubule-Associated Proteins / genetics
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Mitosis / drug effects
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Phosphorylation
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Retinoblastoma Protein / metabolism
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Thyroid Neoplasms / pathology*
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Tumor Cells, Cultured
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Tumor Suppressor Proteins*
Substances
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Butyrates
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CDKN1A protein, human
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Cell Cycle Proteins
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Cyclin A
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Cyclin B
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Enzyme Inhibitors
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Microtubule-Associated Proteins
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Retinoblastoma Protein
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Tumor Suppressor Proteins
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Cyclin-Dependent Kinase Inhibitor p27
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Protein Serine-Threonine Kinases
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CDC2 Protein Kinase
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CDC2-CDC28 Kinases
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CDK2 protein, human
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases