2-Methoxyestradiol-mediated anti-tumor effect increases osteoprotegrin expression in osteosarcoma cells

Michaela B. Benedikt, Eric W. Mahlum, Kristen L. Shogren, Malayannan Subramaniam, Thomas C. Spelsberg, Michael J. Yaszemski, Avudaiappan Maran

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Osteosarcoma is a bone tumor that frequently develops during adolescence. 2-Methoxyestradiol (2-ME), a naturally occurring metabolite of 17β-estradiol, induces cell cycle arrest and cell death in human osteosarcoma cells. To investigate whether the osteoprotegrin (OPG) protein plays a role in 2-ME actions, we studied the effect of 2-ME treatment on OPG gene expression in human osteosarcoma cells. 2-ME treatment induced OPG gene promoter activity and mRNA levels. Also, Western blot analysis showed that 2-ME treatment increased OPG protein levels in MG63, KHOS, 143B and LM7 osteosarcoma cells by 3-, 1.9-, 2.8-, and 2.5-fold, respectively, but did not affect OPG expression in normal bone cells. In addition, increases in OPG protein levels were observed in osteosarcoma cell culture media after 3 days of 2-ME treatment. The effect of 2-ME on osteosarcoma cells was ligand-specific as parent estrogen, 17β-estradiol and a tumorigenic estrogen metabolite, 16α-hydroxyestradiol, which do not affect osteosarcoma cell cycle and cell death, had no effect on OPG protein expression. Furthermore, cotreating osteosarcoma cells with OPG protein did not further enhance 2-ME-mediated anti-tumor effects. OPG-released in 2-ME-treated cultures led to an increase in osteoblastic activity and a decrease in osteoclast number, respectively. These findings suggest that OPG is not directly involved in 2-ME-mediated anti-proliferative effects in osteosarcoma cells, but rather participates in anti-resorptive functions of 2-ME in bone tumor environment.

Original languageEnglish (US)
Pages (from-to)950-956
Number of pages7
JournalJournal of cellular biochemistry
Issue number5
StatePublished - Apr 1 2010


  • 2-Methoxyestradiol
  • Bone cancer
  • Osteosarcoma

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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