Tautomycetin and tautomycin suppress the growth of medullary thyroid cancer cells via inhibition of glycogen synthase kinase-3beta.
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.
Endocrine Surgery Research Laboratories, Department of Surgery, University of Wisconsin, H4/750 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, USA.
Joel T
JT
Adler
Mackenzie
M
Cook
Yinggang
Y
Luo
Susan C
SC
Pitt
Jianhua
J
Ju
Wenli
W
Li
Ben
B
Shen
Muthusamy
M
Kunnimalaiyaan
Herbert
H
Chen
D017209:Apoptosis / Q000187:drug effects*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015153:Blotting, Western; D002116:Calcitonin / Q000378:metabolism; D018276:Carcinoma, Medullary / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005663:Furans / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008055:Lipids / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D011714:Pyrans / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D014407:Tumor Cells, Cultured
D051792:Basic Helix-Loop-Helix Proteins; D002116:Calcitonin; D004791:Enzyme Inhibitors; D005663:Furans; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D008055:Lipids; D010749:Phosphoprotein Phosphatases; D011714:Pyrans; D034741:RNA, Small Interfering; D013141:Spiro Compounds; C065500:ASCL1 protein, human; C053079:tautomycin; C058744:tautomycetin; C000605506:GSK3B protein, human