2-Methoxyestradiol-induced cell death in osteosarcoma cells is preceded by cell cycle arrest

Avudaiappan Maran, Kristen L. Shogren, Michaela Benedikt, Gobinda Sarkar, Russell T. Turner, Michael J. Yaszemski

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

2-Methoxyestradiol (2-ME), a naturally occurring mammalian metabolite of 17β-Estradiol (E2), induces cell death in osteosarcoma cells. To further understand the molecular mechanisms of action, we have investigated cell cycle progression in 2-ME-treated human osteosarcoma (MG63, SaOS-2 and LM8) cells. At 5 μM, 2-ME induced growth arrest by inducing a block in cell cycle; 2-ME-treatment resulted in 2-fold increases in G1 phase cells and a decrease in S phase cells in MG63 and SaOS-2 osteosarcoma cell lines, compared to the appropriate vehicle controls. 2-ME-treatment induced a threefold increase in the G2 phase in LM8 osteosarcoma cells. The results demonstrated steroid specificity, as the tumorigenic metabolite, 16α-hydroxyestradiol (16-OHE), did not have any effect on cell cycle progression in osteosarcoma cells. The cell cycle arrest coincided with an increase in expression of the cell cycle markers p21, p27 and p53 proteins in 2-ME-treated osteosarcoma cells. Also, MG63 cells, transiently transfected with cDNA for a 'loss of function mutant' RNA-dependent protein kinase (PKR) protein, were resistant to 2-ME-induced cell cycle arrest. These results suggest that 2-ME works in concert with factors regulating eel I cycle progression, and cell cycle arrest precedes eel I death in 2-ME-treated osteosarcoma cells.

Original languageEnglish (US)
Pages (from-to)1937-1945
Number of pages9
JournalJournal of cellular biochemistry
Volume104
Issue number5
DOIs
StatePublished - Aug 1 2008

Keywords

  • Cell cycle arrest
  • Estrogen metabolite
  • MG63 cells
  • PKR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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