title: High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor.
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.
authors.affiliation: Department of Breast Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, P.R. China.|Ontario Cancer Institute and The Endocrine Oncology Site Group, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Breast Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, P.R. China.|Ontario Cancer Institute and The Endocrine Oncology Site Group, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada.
authors.forename: Zhaoying
authors.initials: Z
authors.lastname: Yang
authors.affiliation: SMART Laboratory for High-Throughput Screening Programs, Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Letizia
authors.initials: L
authors.lastname: Granieri
authors.affiliation: SMART Laboratory for High-Throughput Screening Programs, Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Adrian
authors.initials: A
authors.lastname: Pasculescu
authors.affiliation: SMART Laboratory for High-Throughput Screening Programs, Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Toronto, ON, Canada.|Department of Agricultural, Food, and Environmental Sciences, University of Perugia, Perugia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Datti
authors.affiliation: Ontario Cancer Institute and The Endocrine Oncology Site Group, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, Toronto, ON, Canada.
authors.forename: Sylvia L
authors.initials: SL
authors.lastname: Asa
authors.affiliation: Department of Breast Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, P.R. China.|Ontario Cancer Institute and The Endocrine Oncology Site Group, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada.
authors.forename: Zheli
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Ontario Cancer Institute and The Endocrine Oncology Site Group, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada.|Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Shereen
authors.initials: S
authors.lastname: Ezzat
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D050257:Tubulin Modulators / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D047428:Protein Kinase Inhibitors; D050257:Tubulin Modulators; D003078:Colchicine
keywords: BRAF; BRAF resistance; colchicine; high throughput drug screening; thyroid cancer