Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Apoptosis / drug effects*
-
Basic Helix-Loop-Helix Transcription Factors / metabolism
-
Blotting, Western
-
Calcitonin / metabolism
-
Carcinoma, Medullary / drug therapy
-
Carcinoma, Medullary / enzymology
-
Carcinoma, Medullary / pathology*
-
Cell Proliferation / drug effects*
-
Enzyme Inhibitors / pharmacology
-
Enzyme-Linked Immunosorbent Assay
-
Furans / pharmacology*
-
Glycogen Synthase Kinase 3 / antagonists & inhibitors*
-
Glycogen Synthase Kinase 3 / genetics
-
Glycogen Synthase Kinase 3 / metabolism
-
Glycogen Synthase Kinase 3 beta
-
Humans
-
Lipids / pharmacology*
-
Phosphoprotein Phosphatases / antagonists & inhibitors
-
Pyrans / pharmacology*
-
RNA, Small Interfering / pharmacology
-
Spiro Compounds / pharmacology*
-
Thyroid Neoplasms / drug therapy
-
Thyroid Neoplasms / enzymology
-
Thyroid Neoplasms / pathology*
-
Tumor Cells, Cultured
Substances
-
ASCL1 protein, human
-
Basic Helix-Loop-Helix Transcription Factors
-
Enzyme Inhibitors
-
Furans
-
Lipids
-
Pyrans
-
RNA, Small Interfering
-
Spiro Compounds
-
tautomycin
-
tautomycetin
-
Calcitonin
-
GSK3B protein, human
-
Glycogen Synthase Kinase 3 beta
-
Glycogen Synthase Kinase 3
-
Phosphoprotein Phosphatases