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High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor.
- Source :
-
Oncotarget [Oncotarget] 2016 Apr 12; Vol. 7 (15), pp. 19948-59. - Publication Year :
- 2016
-
Abstract
- We employed a high-throughput drug library screening platform to identify novel agents affecting thyroid cancer cells. We used human thyroid cancer cell lines to screen a collection of approximately 5200 small molecules with biological and/or pharmacologial properties. Parallel primary screens yielded a number of hits differentially active between thyroid and melanoma cells. Amongst compounds specifically targeting thyroid cancer cells, colchicine emerged as an effective candidate. Colchicine inhibited cell growth which correlated with G2 cell cycle arrest and apoptosis. These effects were hampered through inhibition of MEK1/2 and JNK. In contrast, inhibition of p38-MAPK had little effect, and AKT had no impact on colchicine action. Systemic colchicine inhibited thyroid cancer progression in xenografted mice. These findings demonstrate that our screening platform is an effective vehicle for drug reposition and show that colchicine warrants further attention in well-defined clinical niches such as thyroid cancer.
- Subjects :
- Animals
Apoptosis drug effects
Cell Cycle drug effects
Humans
Mice
Mice, SCID
Protein Kinase Inhibitors pharmacology
Signal Transduction drug effects
Thyroid Neoplasms metabolism
Thyroid Neoplasms pathology
Tumor Cells, Cultured
Colchicine pharmacology
High-Throughput Screening Assays
Thyroid Neoplasms drug therapy
Tubulin Modulators pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 26942566
- Full Text :
- https://doi.org/10.18632/oncotarget.7890