Tautomycetin and tautomycin suppress the growth of medullary thyroid cancer cells via inhibition of glycogen synthase kinase-3beta. Mol Cancer Ther 2009 Apr;8(4):914-20
Date
04/18/2009Pubmed ID
19372564Pubmed Central ID
PMC2670470DOI
10.1158/1535-7163.MCT-08-0712Scopus ID
2-s2.0-66449115520 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
Medullary thyroid cancer (MTC) is a relatively uncommon neuroendocrine tumor that arises from the calcitonin-secreting parafollicular cells of the thyroid gland. Unfortunately, MTC frequently metastasizes, precluding curative surgical resection and causing significant morbidity. Thus, there is an urgent need for new treatment modalities. Tautomycin and tautomycetin are antifungal antibiotics isolated from Streptomyces spiroverticillatus and Streptomyces griseochromogens, respectively. Glycogen synthase kinase-3beta is a serine/threonine protein kinase that regulates multiple cellular processes and is important in various cancers, including MTC. Treatment with tautomycin and tautomycetin decreased neuroendocrine markers, suppressed hormonal secretion, and inhibited growth through apoptosis in MTC cells. Importantly, we describe a novel action of these compounds: inhibition of glycogen synthase kinase-3beta.
Author List
Adler JT, Cook M, Luo Y, Pitt SC, Ju J, Li W, Shen B, Kunnimalaiyaan M, Chen HMESH terms used to index this publication - Major topics in bold
ApoptosisBasic Helix-Loop-Helix Transcription Factors
Blotting, Western
Calcitonin
Carcinoma, Medullary
Cell Proliferation
Enzyme Inhibitors
Enzyme-Linked Immunosorbent Assay
Furans
Glycogen Synthase Kinase 3
Glycogen Synthase Kinase 3 beta
Humans
Lipids
Phosphoprotein Phosphatases
Pyrans
RNA, Small Interfering
Spiro Compounds
Thyroid Neoplasms
Tumor Cells, Cultured