Lestaurtinib is a potent inhibitor of anaplastic thyroid cancer cell line models.

Abstract

Anaplastic thyroid cancer (ATC) is a rare and lethal human malignancy with no known effective therapies in the majority of cases. Despite the use of conventional treatments such as chemotherapy, radiation and surgical resection, this disease remains almost universally fatal. In the present study, we identified the JAK2 inhibitor Lestaurtinib as a potent compound when testing against 13 ATC cell lines. Lestaurtinib demonstrated a potent antiproliferative effect in vitro at nanomolar concentrations. Furthermore, Lestaurtinib impeded cell migration and the ability to form colonies from single cells using scratch-wound and colony formation assays, respectively. Flow cytometry was used for cell cycle analysis following drug treatment and demonstrated arrest at the G2/M phase of the cell cycle, indicative of a cytostatic effect. In vivo studies using the chick chorioallantoic membrane xenograft models demonstrated that treatment with Lestaurtinib resulted in a significant decrease in endpoint tumor volume and vascularity using power Doppler ultrasound imaging. Overall, this study provides evidence that Lestaurtinib is a potent antiproliferative agent with potential antiangiogenic activity that warrants further investigation as a targeted therapy for ATC.

• Authors: Nicole Pinto, Stephenie D Prokopec, Frederick Vizeacoumar, Karlee Searle, Matthew Lowerison, Kara M Ruicci, John Yoo, Kevin Fung, Danielle MacNeil, Jim C Lacefield, Hon S Leong, Joe S Mymryk, John W Barrett, Alessandro Datti, Paul C Boutros, Anthony C Nichols
• Journal: PloS one (PLoS One) Vol. 13 Issue 11 Pg. e0207152 ( 2018) ISSN: 1932-6203 [Electronic] United States
• PMID: 30419054 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Carbazoles
• Furans
• lestaurtinib
• Janus Kinase 2

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Carbazoles (pharmacology)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Chick Embryo
• Dose-Response Relationship, Drug
• Furans
• Humans
• Janus Kinase 2 (metabolism)
• Thyroid Carcinoma, Anaplastic (blood supply, diagnostic imaging, drug therapy)
• Thyroid Neoplasms (blood supply, drug therapy)
• Xenograft Model Antitumor Assays