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KMID : 0356620100250010028
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Journal of Korean Society of Endocrinology
2010 Volume.25 No. 1 p.28 ~ p.36
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Effects of α-lipoic Acid on Differentiation of Thyroid Cancer Cells
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Kim Won-Gu
Choi Hyun-Jeogn
Kim Won-Bae
Han Doo-Hee
Kim Eui-Young
Kim Tae-Yong
Shong Young-Kee
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Abstract
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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 α-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-α 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.
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KEYWORD
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Cancer, Differentiation, Lipoic acid, Thyroglobulin, Thyroid
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