The short-chain fatty acid, α-lipoic acid (ALA) is a powerful antioxidant used for treatment of diabetic neuropathy. Recent studies suggested the possibility of ALA as a potential anti-cancer agent, because it could activate adenosine monophosphate activated protein kinase (AMPK) and inhibit transforming growth factor-β (TGFβ) pathway. We evaluate the effects of ALA on thyroid cancer cell proliferation, migration, and invasion. We performed in vitro cell proliferation analysis with BCPAP, HTH-83, CAL-62, and FTC-133 cells. ALA suppressed cell proliferation through activation of AMPK and subsequent down-regulation of mammalian target of rapamycin (mTOR)-S6 signaling pathway. Low-dose ALA, which had minimal effects on cell proliferation, also decreased cell migration and invasion of BCPAP, CAL-62, and HTH-83 cells. ALA inhibited epithelial mesenchymal transition (EMT) evidently by increase of E-cadherin and decreases of activated β-catenin, vimentin, snail, and twist in these cells. ALA suppressed TGFβ production and inhibited induction of p-Smad2, and twist by TGFβ1 or TGFβ2. These findings indicate that ALA reduces thyroid cancer cell migration and invasion through suppression of TGFβ production and inhibition of TGFβ signaling pathways. ALA also significantly suppressed tumor growth in mouse xenograft model using BCPAP and FTC-133 cells. This is the first study to show anti-cancer effect of ALA on thyroid cancer cells. ALA could be a potential therapeutic agent for advanced thyroid cancer, as an adjuvant therapy with other systemic therapeutic agents.
Citation Format: Hyemi Kwon, Min Ji Jeon, Won Gu Kim, Seonhee Lim, Soyoung Sim, Tae Yong Kim, Young Kee Shong, Won Bae Kim. Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1816.