Alpha-lipoic acid induces sodium iodide symporter expression in TPC-1 thyroid cancer cell line

Nucl Med Biol. 2012 Nov;39(8):1275-80. doi: 10.1016/j.nucmedbio.2012.08.007. Epub 2012 Sep 18.

Abstract

Introduction: Patients with metastatic thyroid cancers that do not uptake iodine need effective therapeutic option. Differentiation-inducing agents have been tried to restore functional expression of sodium iodide symporter (NIS) without success. Our objective was to assess the effect of alpha-lipoic acid (ALA), known as potential antioxidant, on expression of sodium iodide symporter in thyroid cancer cells.

Methods: Human thyroid cancer-derived cell lines, TPC-1, were treated with ALA, and changes in NIS mRNA and protein expression were measured. ALA's effect on NIS gene promoter was evaluated, and functional NIS expression was assessed by iodide uptake assay.

Results: Treatment with ALA increased NIS mRNA expression up to ten folds of control dose-dependently after 24 h of exposure. ALA increased NIS promoter activity, and increased iodide uptake by 1.6 fold. ALA induced expression of NIS protein, but had no significant effect on the plasma membrane trafficking. ALA increased phosphorylation of CREB and nuclear translocation of pCREB, and co-treatment of ALA and trichostatin A increased iodide uptake by three folds in TPC-1 cells.

Conclusions: ALA is a potential agent to increase NIS transcription in TPC-1. It could be used as an adjunctive agent to increase efficacy of radioiodine therapy if combined with a strategy to increase NIS protein trafficking to cell membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Proliferation / drug effects
  • Drug Synergism
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Iodides / metabolism
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / genetics
  • Protein Transport / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Symporters / genetics*
  • Symporters / metabolism*
  • Thioctic Acid / pharmacology*
  • Thyroid Neoplasms / pathology*

Substances

  • Antioxidants
  • Iodides
  • RNA, Messenger
  • Reactive Oxygen Species
  • Symporters
  • sodium-iodide symporter
  • Thioctic Acid