Τίτλος:
Mechanisms of the action of zoledronic acid on human MG-63 osteosarcoma cells
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © Georg Thieme Verlag KG Stuttgart.
Συγγραφείς:
Tenta, R.
Pitulis, N.
Tiblalexi, D.
Consoulas, C.
Katopodis, H.
Konstantinidou, E.
Manoussakis, M.
Kletsas, D.
Alexis, M.N.
Poyatzi, A.
Koutsilieris, M.
Περιοδικό:
Hormone and Metabolic Research
Λέξεις-κλειδιά:
3 (4,5 dimethyl 2 thiazolyl) 2,5 diphenyltetrazolium bromide; doxorubicin; edetic acid; estrogen receptor alpha; farnesyl diphosphate; geranylgeranyl pyrophosphate; Ras protein; trypan blue; zoledronic acid, article; calcium cell level; cancer cell culture; cell cycle G0 phase; cell cycle G1 phase; cell death; cell proliferation; cellular distribution; controlled study; dose response; drug antagonism; drug mechanism; flow cytometry; human; human cell; osteosarcoma cell; priority journal; protein expression; reverse transcription polymerase chain reaction, Aniline Compounds; Apoptosis; Calcium; Cell Differentiation; Cell Division; Cell Line, Tumor; Diphosphonates; Doxorubicin; Edetic Acid; Flow Cytometry; Fluorescent Dyes; G0 Phase; G1 Phase; Humans; Imidazoles; Osteosarcoma; Polyisoprenyl Phosphates; ras Proteins; Receptors, Estrogen; Reverse Transcriptase Polymerase Chain Reaction; Sesquiterpenes; Xanthenes
DOI:
10.1055/s-2008-1078753
