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.
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.
Authors: Y J Ko; E J Small; F Kabbinavar; A Chachoua; S Taneja; D Reese; A DePaoli; A Hannah; S P Balk; G J Bubley Journal: Clin Cancer Res Date: 2001-04 Impact factor: 12.531
Authors: Rebecca S Sippel; Jennifer E Carpenter; Muthusamy Kunnimalaiyaan; Sara Lagerholm; Herbert Chen Journal: Am J Physiol Gastrointest Liver Physiol Date: 2003-08 Impact factor: 4.052
Authors: Edmond F O'Donnell; Katerine S Saili; Daniel C Koch; Prasad R Kopparapu; David Farrer; William H Bisson; Lijoy K Mathew; Sumitra Sengupta; Nancy I Kerkvliet; Robert L Tanguay; Siva Kumar Kolluri Journal: PLoS One Date: 2010-10-01 Impact factor: 3.240
Authors: Edmond F O'Donnell; Prasad Rao Kopparapu; Daniel C Koch; Hyo Sang Jang; Jessica Lynne Phillips; Robert L Tanguay; Nancy I Kerkvliet; Siva Kumar Kolluri Journal: PLoS One Date: 2012-07-17 Impact factor: 3.240