Mebendazole Inhibits Tumor Growth and Prevents Lung Metastasis in Models of Advanced Thyroid Cancer

Details

• Personal Author:
  Cerutti JM ; Joe N ; Mendes TB ; Riggins GJ ; Williamson T
• Description:
  The most common thyroid malignancy is papillary thyroid cancer. While a majority respond to therapy and have a favorable prognosis, some papillary thyroid cancers persist. This subset may dedifferentiate to anaplastic thyroid cancer, an aggressive, highly invasive and rapidly fatal cancer. Thyroid cancer patients at risk for disease progression and metastasis need earlier, safer and more effective therapies. The purpose of this translational study was to determine if mebendazole could be repurposed to effectively treat thyroid cancer, in particular before metastasis. In vitro, mebendazole potently inhibited the growth of a panel of human papillary and anaplastic thyroid cancer cells. In papillary (B-CPAP) and anaplastic (8505c) cell lines, mebendazole increased the percentage of cells in G2/M cell cycle arrest and induced late stage apoptosis by activation of the caspase-3 pathway. In aggressive 8505c cells, mebendazole significantly repressed migratory and invasive potential in a wound healing and transwell invasion assay and inhibited expression of phosphorylated Akt and Stat3 and reduced Gli1. In vivo, mebendazole treatment resulted in significant orthotopic thyroid tumor regression (B-CPAP) and growth arrest (8505c), with treated tumors displaying reduced expression of the proliferation maker KI67 and less vascular epithelium as indicated by CD31+ immunohistochemistry. Most importantly, daily oral mebendazole prevented established thyroid tumors from metastasizing to the lung. Given the low toxicity and published anticancer mechanisms of mebendazole, this novel preclinical study of mebendazole in thyroid cancer has promising therapeutic implications for patients with treatment refractory papillary or anaplastic thyroid cancer. [Description provided by NIOSH]
• Subjects:
  Lung Diseases Neoplasms Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Author Keywords: Mebendazole BRAFV600E Mutation Cancer Carcinomas Cell Proliferation Endocrine System Disorders Lung Disease Lung Metastasis Medical Treatment Medicinal Chemicals Metastatic Disease Papillary Thyroid Carcinoma Thyroid Gland Disorders Undifferentiated Anaplastic Thyroid Carcinoma

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• ISSN:
  1351-0088
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; New York ; OSHA Region 2 ; OSHA Region 3
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  123-136
• Volume:
  27
• Issue:
  3
• NIOSHTIC Number:
  nn:20061826
• Citation:
  Endocr Relat Cancer 2020 Mar; 27(3):123-136
• Contact Point Address:
  Gregory J Riggins, Departments of Neurosurgery and Oncology, Johns Hopkins University, Baltimore, Maryland, USA
• Email:
  griggin1@jhmi.edu
• CAS Registry Number:
  Mebendazole (CAS RN 31431-39-7)
• Federal Fiscal Year:
  2020
• Performing Organization:
  Icahn School of Medicine at Mount Sinai, New York
• Peer Reviewed:
  True
• Start Date:
  20160901
• Source Full Name:
  Endocrine-Related Cancer
• End Date:
  20190831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e4b45174efd79a981c9d0197e2c7ba932d975bad68ecb65d874b94d782a991fb06a6bb22a297641e4c6e594d691c4b358cd398e993c326a12820e9043e30dbd1
• Download URL:
  https://stacks.cdc.gov/view/cdc/225199/cdc_225199_DS1.pdf
• File Type:
  [PDF - 2.38 MB ]