PMID- 26463583
OWN - NLM
STAT- MEDLINE
DCOM- 20161006
LR  - 20211203
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 419
DP  - 2016 Jan 5
TI  - Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of 
      thyroid cancer cells.
PG  - 113-23
LID - S0303-7207(15)30106-4 [pii]
LID - 10.1016/j.mce.2015.10.005 [doi]
AB  - The naturally occurring short-chain fatty acid, alpha-lipoic acid (ALA) is a powerful 
      antioxidant which is clinically 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-beta (TGFbeta) pathway. In this study, we 
      evaluate the effects of ALA on thyroid cancer cell proliferation, migration and 
      invasion. We performed in vitro cell proliferation analysis using BCPAP, HTH-83, 
      CAL-62 and FTC-133 cells. ALA suppressed thyroid cancer 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 beta-catenin, vimentin, snail, 
      and twist in these cells. ALA suppressed TGFbeta production and inhibited induction 
      of p-Smad2 and twist by TGFbeta1 or TGFbeta2. These findings indicate that ALA reduces 
      cancer cell migration and invasion through suppression of TGFbeta production and 
      inhibition of TGFbeta signaling pathways in thyroid cancer cells. 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 treatment of 
      advanced thyroid cancer, possibly as an adjuvant therapy with other systemic 
      therapeutic agents.
CI  - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
FAU - Jeon, Min Ji
AU  - Jeon MJ
AD  - Department of Internal Medicine, Asan Medical Center, University of Ulsan College 
      of Medicine, Seoul, South Korea.
FAU - Kim, Won Gu
AU  - Kim WG
AD  - Department of Internal Medicine, Asan Medical Center, University of Ulsan College 
      of Medicine, Seoul, South Korea.
FAU - Lim, Seonhee
AU  - Lim S
AD  - Asan Institute of Life Sciences, Seoul, South Korea.
FAU - Choi, Hyun-Jeung
AU  - Choi HJ
AD  - Asan Institute of Life Sciences, Seoul, South Korea.
FAU - Sim, Soyoung
AU  - Sim S
AD  - Asan Institute of Life Sciences, Seoul, South Korea.
FAU - Kim, Tae Yong
AU  - Kim TY
AD  - Department of Internal Medicine, Asan Medical Center, University of Ulsan College 
      of Medicine, Seoul, South Korea.
FAU - Shong, Young Kee
AU  - Shong YK
AD  - Department of Internal Medicine, Asan Medical Center, University of Ulsan College 
      of Medicine, Seoul, South Korea.
FAU - Kim, Won Bae
AU  - Kim WB
AD  - Department of Internal Medicine, Asan Medical Center, University of Ulsan College 
      of Medicine, Seoul, South Korea. Electronic address: kimwb@amc.seoul.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151014
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Transforming Growth Factor beta)
RN  - 73Y7P0K73Y (Thioctic Acid)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics/metabolism
MH  - Animals
MH  - Antineoplastic Agents/*administration & dosage/pharmacology
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Epithelial-Mesenchymal Transition/*drug effects
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Mice
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - Thioctic Acid/*administration & dosage/pharmacology
MH  - Thyroid Neoplasms/*drug therapy/genetics/metabolism
MH  - Transforming Growth Factor beta/genetics/metabolism
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - Alpha lipoic acid
OT  - Epithelial-mesenchymal transition
OT  - Transforming growth factor beta
EDAT- 2015/10/16 06:00
MHDA- 2016/10/08 06:00
CRDT- 2015/10/15 06:00
PHST- 2015/04/03 00:00 [received]
PHST- 2015/08/31 00:00 [revised]
PHST- 2015/10/06 00:00 [accepted]
PHST- 2015/10/15 06:00 [entrez]
PHST- 2015/10/16 06:00 [pubmed]
PHST- 2016/10/08 06:00 [medline]
AID - S0303-7207(15)30106-4 [pii]
AID - 10.1016/j.mce.2015.10.005 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2016 Jan 5;419:113-23. doi: 10.1016/j.mce.2015.10.005. Epub 
      2015 Oct 14.