Evodiamine Suppresses Survival, Proliferation, Migration and Epithelial-Mesenchymal Transition of Thyroid Carcinoma Cells

Anticancer Res. 2018 Nov;38(11):6339-6352. doi: 10.21873/anticanres.12992.

Abstract

Background/aim: The aim of this study was to evaluate the effect of evodiamine alone or in combination with chemotherapeutic agents on thyroid carcinoma cells.

Materials and methods: TPC-1 and SW1736 thyroid carcinoma cells were used. Cell viability, cytotoxic activity, apoptosis and migration were examined by applying appropriate methods. Drug combination analysis was performed.

Results: Evodiamine treatment of cells decreased cell viability, and Bcl2 and phospho-AKT protein levels. Cytotoxic activity and the percentage of apoptotic cells increased. After co-treatment of wortmannin, cell viability, and phospho-AKT and Bcl2 protein levels decreased, and cytotoxic activity increased. In transforming growth factor-β-treated cells, evodiamine attenuated variations in morphology, growth and migration, and increased p21 and p53 protein levels, and decreased β-catenin, N-cadherin, vimentin, phospho-AKT, matrix metalloproteinase-2 and matrix metalloproteinase-9 protein levels. When cells were treated with both evodiamine and chemotherapeutic agents, all combination index values were lower than 1.0.

Conclusion: Evodiamine was cytotoxic towards thyroid carcinoma cells, and repression of AKT reinforced evodiamine-induced cytotoxicity. Furthermore, evodiamine ameliorated proliferation, migration and epithelial-mesenchymal transition, and synergized with chemotherapeutic agents.

Keywords: AKT; Thyroid carcinoma; chemotherapeutic agent; evodiamine; synergism.

MeSH terms

  • Androstadienes / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Synergism
  • Epithelial-Mesenchymal Transition / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Quinazolines / pharmacology*
  • Signal Transduction / drug effects
  • Thyroid Neoplasms / drug therapy
  • Thyroid Neoplasms / metabolism*
  • Wortmannin

Substances

  • Androstadienes
  • Antineoplastic Agents
  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Quinazolines
  • evodiamine
  • Proto-Oncogene Proteins c-akt
  • Wortmannin