caa a22 4500 477127991 CHVBK 20180405111655.0 cr unu---uuuuu 170330e19970501xx s 000 0 eng 10.1023/A:1012157212793 doi (NATIONALLICENCE)springer-10.1023/A:1012157212793 Inhibition of Growth of Dictyostelium discoideum Amoebae by Bisphosphonate Drugs Is Dependent on Cellular Uptake [Elektronische Daten] [Michael Rogers, Xiaojuan Xiong, Xiaohui Ji, Jukka Mönkkönen, R. Russell, Michael Williamson, Frank Ebetino, Donald Watts] Purpose. The aim of the study was to determine whether bisphosphonates are internalised by Dictyosteliumamoebae and whether cellular uptake is required for their growth-inhibitory effects. Bisphosphonates inhibit growth of amoebae of the slime mould Dictyostelium discoideum, by mechanisms that appear to be similar to those that cause inhibition of osteoclastic bone resorption. Methods. Cell-free extracts prepared from amoebae that had been incubated with bisphosphonates were analysed by 3lP-n.m.r. spectroscopy or ion-exchange f.p.l.c., to identify the presence of bisphosphonates or bisphosphonate metabolites respectively. The growth-inhibitory effect of bisphosphonates towards Dictyostelium amoebae was also examined under conditions in which pinocytosis was inhibited. Results. All of the bisphosphonates studied were internalised by Dictyostelium amoebae, probably by fluid-phase pinocytosis, and could be detected in cell-free extracts. Amoebae that were prevented from internalising bisphosphonates by pinocytosis were markedly resistant to the growth-inhibitory effects of these compounds. In addition, bisphosphonates encapsulated within liposomes were more potent growth inhibitors of Dictyostelium owing to enhanced intracellular delivery of bisphosphonates. Conclusions. All bisphosphonates inhibit Dictyostelium growth by intracellular mechanisms following internalisation of bisphosphonates by fluid-phase pinocytosis. It is therefore likely that bisphosphonates also affect osteoclasts by interacting with intracellular, rather than extracellular, processes. Plenum Publishing Corporation, 1997 bisphosphonates nationallicence Dictyostelium nationallicence endocytosis nationallicence growth inhibition nationallicence 31P-n.m.r nationallicence osteoclasts nationallicence Rogers Michael Institute for Bone and Joint Medicine, Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, UK aut Xiong Xiaojuan Department of Molecular Biology and Biotechnology, University of Sheffield, Krebs Institute, Firth Court, Western Bank, PO Box 594, S10 2UH, Sheffield, UK aut Ji Xiaohui Department of Molecular Biology and Biotechnology, University of Sheffield, Krebs Institute, Firth Court, Western Bank, PO Box 594, S10 2UH, Sheffield, UK aut Mönkkönen Jukka Department of Pharmaceutics, University of Kuopio, Finland aut Russell R. Institute for Bone and Joint Medicine, Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, UK aut Williamson Michael Department of Molecular Biology and Biotechnology, University of Sheffield, Krebs Institute, Firth Court, Western Bank, PO Box 594, S10 2UH, Sheffield, UK aut Ebetino Frank Procter & Gamble Pharmaceuticals, Cincinnati, Ohio aut Watts Donald Department of Molecular Biology and Biotechnology, University of Sheffield, Krebs Institute, Firth Court, Western Bank, PO Box 594, S10 2UH, Sheffield, UK aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 625-630 0724-8741 14:5<625 1997 14 11095 https://doi.org/10.1023/A:1012157212793 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012157212793 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rogers Michael Institute for Bone and Joint Medicine, Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, UK aut NATIONALLICENCE 700 1- Xiong Xiaojuan Department of Molecular Biology and Biotechnology, University of Sheffield, Krebs Institute, Firth Court, Western Bank, PO Box 594, S10 2UH, Sheffield, UK aut NATIONALLICENCE 700 1- Ji Xiaohui Department of Molecular Biology and Biotechnology, University of Sheffield, Krebs Institute, Firth Court, Western Bank, PO Box 594, S10 2UH, Sheffield, UK aut NATIONALLICENCE 700 1- Mönkkönen Jukka Department of Pharmaceutics, University of Kuopio, Finland aut NATIONALLICENCE 700 1- Russell R. Institute for Bone and Joint Medicine, Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, UK aut NATIONALLICENCE 700 1- Williamson Michael Department of Molecular Biology and Biotechnology, University of Sheffield, Krebs Institute, Firth Court, Western Bank, PO Box 594, S10 2UH, Sheffield, UK aut NATIONALLICENCE 700 1- Ebetino Frank Procter & Gamble Pharmaceuticals, Cincinnati, Ohio aut NATIONALLICENCE 700 1- Watts Donald Department of Molecular Biology and Biotechnology, University of Sheffield, Krebs Institute, Firth Court, Western Bank, PO Box 594, S10 2UH, Sheffield, UK aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 625-630 0724-8741 14:5<625 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer