Endocrinol Metab > Volume 25(1); 2010 > Article
Journal of Korean Endocrine Society 2010;25(1):28-36.
DOI: https://doi.org/10.3803/jkes.2010.25.1.28    Published online March 1, 2010.
Effects of alpha-lipoic Acid on Differentiation of Thyroid Cancer Cells.
Won Gu Kim, Doo Hee Han, Hyun Jeung Choi, Eui Young Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
1Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Korea.
2Asan Institute of Life Sciences, Korea.
3College of Life Sciences and Biotechnology, Korea University, Korea.
Abstract
BACKGROUND
Induction of re-differentiation is necessary for the proper treatment of patients with recurrent or metastatic differentiated thyroid cancer (DTC) because cancer cells show de-differentiation in about 30% of these patients. In this study, we evaluated the expression of thyroid specific genes after treatment with various agents to induce re-differentiation in the follicular thyroid cancer cell line FTC-133. METHODS: FTC-133 cells were treated with U0126, LY294002, trichostatin A, retinoic acid (RA), 5'-azacytidine and alpha-lipoic acid (ALA). We evaluated mRNA expression of thyroid specific genes, thyroglobulin (Tg), sodium iodine symporter (NIS), PAX-8 and TTF-1 by reverse transcriptase polymerase chain reaction (PCR). Quantified expression of Tg mRNA was also evaluated by real-time PCR. RESULTS: The expression of Tg mRNA increased after 48 h of treatment with 0.1 uM RA and the expression of Tg mRNA and TTF-1 mRNA increased after 48-72 h of treatment with ALA (10~100 uM). There was no change in thyroid specific gene expression by the other agents. Increased expression of Tg mRNA was confirmed by real-time PCR (1.3 times by 10 uM ALA and 3.6 times by 100 uM ALA). There was no basal NIS mRNA expression in FTC-133 cells and none of the tested agents induced expression of NIS mRNA. There was no change in phosphorylation of AMPK1-alpha after ALA treatment of FTC-133 cells. CONCLUSION: ALA increases mRNA expression of Tg and TTF-1 of FTC-133 thyroid cancer cells and these effects are not mediated by activation of AMP kinase. The finding that ALA could be a potential re-differentiation inducing agent in thyroid cancer cells is novel. Further studies are needed to elucidate the mechanism of induction of re-differentiation. Furthermore, the effect of ALA on NIS expression and on iodine uptake should be evaluated using diverse thyroid cancer cell lines.
Key Words: Cancer, Differentiation, Lipoic acid, Thyroglobulin, Thyroid


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