Horm Metab Res 2008; 40(11): 737-745
DOI: 10.1055/s-2008-1078753
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Mechanisms of the Action of Zoledronic Acid on Human MG-63 Osteosarcoma Cells

R. Tenta 1 , N. Pitulis 1 , D. Tiblalexi 1 , C. Consoulas 1 , H. Katopodis 1 , E. Konstantinidou 1 , M. Manoussakis 2 , D. Kletsas 3 , M. N. Alexis 4 , A. Poyatzi 1 , M. Koutsilieris 1
  • 1Department of Experimental Physiology, Medical School, University of Athens, Goudi-Athens Greece
  • 2Department of Pathophysiology, Medical School, University of Athens, Goudi-Athens Greece
  • 3Laboratory of Cell Proliferation and Ageing, Institute of Biology, National Centre for Scientific Research “Demokritos”, Athens, Greece
  • 4Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece
Further Information

Publication History

received 06.11.2007

accepted 13.03.2008

Publication Date:
18 June 2008 (online)

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Abstract

The aim of our study was to analyze the action of zoledronic acid on MG-63 human osteosarcoma cells. The proliferation of MG-63 cells was inhibited by either continuous or pulsatile exposures of zoledronic acid in a dose-dependent manner (10–250 μM). Zoledronic acid did not produce evidence of MG-63 cell death when administered at 100 mM for 48 hours, but only after exposure of 96 hours. Zoledronic acid (100 μM) increased the distribution of MG-63 cells in G0/G1 phase, however, it did not increase the adriamycin-induced apoptosis. In addition, zoledronic acid action was partially neutralized by exogenous administration of geranylgeranyl pyrophosphate (GGPP), but not by farnesyl pyrophosphate (FPP). Furthermore, zoledronic acid resulted in the attenuation of the prenylated form of Ras. Zoledronic acid and EDTA increased fluorescence of Fluo-3 loaded MG-63 cells in a similar pattern. This increase was owing to the release of Ca2+from intracellular stores since zoledronic acid failed to reveal such a change to intracellular Ca2+when cells were previously treated with 1 mM caffeine. Moreover, zoledronic acid significantly decreased the expression of estrogen receptor α (ERα) whereas it did not change significantly the expression of estrogen receptor β (ERβ) in MG-63 cells. These data suggest that zoledronic acid can control the proliferation and the differentiation of osteosarcoma-like cells.

References

Correspondence

M. KoutsilierisMD, PhD 

Department of Experimental Physiology

Medical School

University of Athens

75 Micras Asias

11527 Goudi-Athens

Greece

Phone: +30/210/746 25 97

Fax: +30/210/746 25 71

Email: mkoutsil@med.uoa.gr