2. Academic Validation
  3. Lestaurtinib is a potent inhibitor of anaplastic thyroid cancer cell line models

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

  • PLoS One. 2018 Nov 12;13(11):e0207152. doi: 10.1371/journal.pone.0207152.
Nicole Pinto 1 2,  Stephenie D Prokopec 3,  Frederick Vizeacoumar 4,  Karlee Searle 5,  Matthew Lowerison 6,  Kara M Ruicci 1,  John Yoo 1,  Kevin Fung 1,  Danielle MacNeil 1,  Jim C Lacefield 6,  Hon S Leong 7,  Joe S Mymryk 8 9,  John W Barrett 1 8,  Alessandro Datti 10 11,  Paul C Boutros 3 12 13,  Anthony C Nichols 1 8
Affiliations

Affiliations

  • 1 Department of Otolaryngology-Head and Neck Surgery, Western University, London, Ontario, Canada.
  • 2 Department of Anatomy and Cell Biology, Western University, London, Ontario, Canada.
  • 3 Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
  • 4 Cancer Research Cluster, University of Saskatchewan, Saskatchewan, Canada.
  • 5 Western University, London, Ontario, Canada.
  • 6 Department of Medical Biophysics, Western University, London, Ontario, Canada.
  • 7 Department of Urology, Mayo Clinic, Rochester, Minnesota, United States of America.
  • 8 Department of Oncology, Western University, London, Ontario, Canada.
  • 9 Department of Microbiology and Immunology, Western University, London, Ontario, Canada.
  • 10 Network Biology Collaborative Centre, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
  • 11 Department of Agricultural, Food, and Environmental Sciences, University of Perugia, Perugia, Italy.
  • 12 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • 13 Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.
PMID: 30419054 DOI: 10.1371/journal.pone.0207152
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.

Figures
Products