Melatonin suppresses epithelial‑to‑mesenchymal transition in the MG‑63 cell line

Mol Med Rep. 2020 Mar;21(3):1356-1364. doi: 10.3892/mmr.2019.10902. Epub 2019 Dec 23.

Abstract

Epithelial‑to‑mesenchymal transition (EMT) is a major process involved in tumor progression and metastasis. Melatonin is secreted by the pineal gland and has been documented as a potential therapeutic agent for multiple tumors. However, the effects of melatonin on EMT during osteosarcoma (OA) development remain undefined. The present study explored the biological functions and effects of melatonin on EMT induced by transforming growth factor β1 (TGF‑β1) and its underlying mechanisms in MG‑63 cells. Using western‑blotting and immunofluorescence, it was found that the switch in E‑cadherin/N‑cadherin and vimentin expression was induced by TGF‑β1, which was reversed by melatonin through the suppression of Snail and matrix metalloproteinase 9 (MMP‑9), through hypoxia‑inducible factor 1α (HIF‑1α) inhibition. These findings demonstrated that the anticancer effects of melatonin against OA MG‑63 cells is through the suppression of EMT via HIF‑1α/Snail/MMP‑9 signaling.

Keywords: MG-63; epithelial-to-mesenchymal transition; melatonin; transforming growth factor β1; osteosarcoma.

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Melatonin / pharmacology*
  • Osteosarcoma / pathology
  • Snail Family Transcription Factors / genetics
  • Snail Family Transcription Factors / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Snail Family Transcription Factors
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Matrix Metalloproteinase 9
  • Melatonin