Leflunomide suppresses growth in human medullary thyroid cancer cells. J Surg Res 2013 Nov;185(1):212-6
Date
07/03/2013Pubmed ID
23816245Pubmed Central ID
PMC3805832DOI
10.1016/j.jss.2013.05.089Scopus ID
2-s2.0-84886722959 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
BACKGROUND: Medullary thyroid cancer (MTC) is a neuroendocrine tumor that arises from the calcitonin-secreting parafollicular cells of the thyroid gland. Leflunomide (LFN) is a disease-modifying antirheumatic drug approved for the treatment of rheumatoid arthritis, and its active metabolite teriflunomide has been identified as a potential anticancer drug. In this study we investigated the ability of LFN to similarly act as an anticancer drug by examining the effects of LFN treatment on MTC cells.
METHODS: Human MTC-TT cells were treated with LFN (25-150 μmol/L) and Western blotting was performed to measure levels of neuroendocrine markers. MTT assays were used to assess the effect of LFN treatment on cellular proliferation.
RESULTS: LFN treatment downregulated neuroendocrine markers ASCL1 and chromogranin A. Importantly, LFN significantly inhibited the growth of MTC cells in a dose-dependent manner.
CONCLUSIONS: Treatment with LFN decreased neuroendocrine tumor marker expression and reduced the cell proliferation in MTC cells. As the safety of LFN in human beings is well established, a clinical trial using this drug to treat patients with advanced MTC may be warranted.
Author List
Alhefdhi A, Burke JF, Redlich A, Kunnimalaiyaan M, Chen HMESH terms used to index this publication - Major topics in bold
Antineoplastic AgentsAntirheumatic Agents
Basic Helix-Loop-Helix Transcription Factors
Biomarkers
Carcinoma, Medullary
Carcinoma, Neuroendocrine
Cell Line, Tumor
Cell Proliferation
Chromogranin A
Dose-Response Relationship, Drug
Down-Regulation
Humans
Isoxazoles
Thyroid Neoplasms