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.
[1]Jilin Univ, China Japan Union Hosp, Dept Breast Surg, Changchun 130023, Jilin, Peoples R China.
[2]Princess Margaret Hosp, Univ Hlth Network, Ontario Canc Inst, Toronto, ON M4X 1K9, Canada.
[3]Princess Margaret Hosp, Univ Hlth Network, Endocrine Oncol Site Grp, Toronto, ON M4X 1K9, Canada.
[4]Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, SMART Lab High Throughput Screening Programs, Toronto, ON M5G 1X5, Canada.
[5]Univ Perugia, Dept Agr Food & Environm Sci, I-06100 Perugia, Italy.
[6]Dept Lab Med, Toronto, ON, Canada.
[7]Dept Pathobiol, Toronto, ON, Canada.
[8]Univ Toronto, Dept Med, Toronto, ON, Canada.
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