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 journalArticle

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Abstract

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
Volume109
Issue number5
DOIs
StatePublished - Apr 1 2010

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Osteosarcoma
Tumors
Neoplasms
Bone
Cell death
Metabolites
Proteins
Bone and Bones
Estradiol
Estrogens
2-methoxyestradiol
Cell Death
Cells
Osteoclasts
Therapeutics
Cell Cycle Checkpoints
Cell culture
Gene expression
Culture Media
Cell Cycle

Keywords

  • 2-Methoxyestradiol
  • Bone cancer
  • OPG. OPGL
  • Osteosarcoma

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Benedikt, M. B., Mahlum, E. W., Shogren, K. L., Subramaniam, M., Spelsberg, T. C., Yaszemski, M. J., & Maran, A. (2010). 2-Methoxyestradiol-mediated anti-tumor effect increases osteoprotegrin expression in osteosarcoma cells. Journal of Cellular Biochemistry, 109(5), 950-956. https://doi.org/10.1002/jcb.22473

2-Methoxyestradiol-mediated anti-tumor effect increases osteoprotegrin expression in osteosarcoma cells. / Benedikt, Michaela B.; Mahlum, Eric W.; Shogren, Kristen L.; Subramaniam, Malayannan; Spelsberg, Thomas C.; Yaszemski, Michael J; Maran, Avudaiappan.

In: Journal of Cellular Biochemistry, Vol. 109, No. 5, 01.04.2010, p. 950-956.

Research output: Contribution to journalArticle

Benedikt, MB, Mahlum, EW, Shogren, KL, Subramaniam, M, Spelsberg, TC, Yaszemski, MJ & Maran, A 2010, '2-Methoxyestradiol-mediated anti-tumor effect increases osteoprotegrin expression in osteosarcoma cells', Journal of Cellular Biochemistry, vol. 109, no. 5, pp. 950-956. https://doi.org/10.1002/jcb.22473
Benedikt, Michaela B. ; Mahlum, Eric W. ; Shogren, Kristen L. ; Subramaniam, Malayannan ; Spelsberg, Thomas C. ; Yaszemski, Michael J ; Maran, Avudaiappan. / 2-Methoxyestradiol-mediated anti-tumor effect increases osteoprotegrin expression in osteosarcoma cells. In: Journal of Cellular Biochemistry. 2010 ; Vol. 109, No. 5. pp. 950-956.
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