The estrogen metabolite 2-methoxyestradiol regulates eukaryotic initiation factor 4E (eIF4E) and inhibits protein synthesis in MG63 osteosarcoma cells

Avudaiappan Maran, Kristen L. Shogren, Michael J. Yaszemski

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Osteosarcoma is a primary bone tumor that affects children and young adults. The estrogen metabolite 2-methoxyestradiol (2-ME) induces cell death in osteosarcoma cells. To determine whether 2-ME actions involve the control of protein synthesis, we studied the effect of 2-ME on eukaryotic initiation factor 4E (eIF4E) and eIF4E-binding protein 1 (4E-BP1) in MG63 osteosarcoma cells. Our results show that 2-ME treatment increases the association of eIF4E with 4E-BP1 in osteosarcoma cells. Also, 2-ME decreases the binding of eIF4E protein to 7-methyl-guanosine cap structure, indicating that 2-ME treatment results in the inhibition of translational initiation. These findings are further supported by the inhibition of protein synthesis in 2-ME-treated osteosarcoma cells. Taken together, our studies show that 2-ME-mediated antitumor effects in osteosarcoma cells involve the regulation of protein synthesis, and translational machinery could serve as a target in the treatment of osteosarcoma.

Original languageEnglish (US)
Pages (from-to)153-158
Number of pages6
JournalGenes and Diseases
Volume3
Issue number2
DOIs
StatePublished - Jun 1 2016

Keywords

  • 2-Methoxyestradiol
  • 4E-BP
  • EIF4E
  • Estrogen metabolite
  • Osteosarcoma

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics(clinical)
  • Cell Biology

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