Medical College of Wisconsin
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Leflunomide suppresses growth in human medullary thyroid cancer cells. J Surg Res 2013 Nov;185(1):212-6

Date

07/03/2013

Pubmed ID

23816245

Pubmed Central ID

PMC3805832

DOI

10.1016/j.jss.2013.05.089

Scopus ID

2-s2.0-84886722959 (requires institutional sign-in at Scopus site)   24 Citations

Abstract

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 H



MESH terms used to index this publication - Major topics in bold

Antineoplastic Agents
Antirheumatic 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