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Titolo:
Nitrogen-containing bisphosphonates induce apoptosis of Caco-2 cells in vitro by inhibiting the mevalonate pathway: A model of bisphosphonate-inducedgastrointestinal toxicity
Autore:
Suri, S; Monkkonen, J; Taskinen, M; Pesonen, J; Blank, MA; Phipps, RJ; Rogers, MJ;
Indirizzi:
Univ Aberdeen, Sch Med, Dept Med & Therapeut, Aberdeen AB25 2ZD, Scotland Univ Aberdeen Aberdeen Scotland AB25 2ZD ut, Aberdeen AB25 2ZD, Scotland Univ Sheffield, Sch Med, Dept Human Metab & Clin Biochem, Sheffield S10 2RX, S Yorkshire, England Univ Sheffield Sheffield S Yorkshire England S10 2RX S Yorkshire, England Univ Kuopio, Dept Pharmaceut, FIN-70211 Kuopio, Finland Univ Kuopio Kuopio Finland FIN-70211 armaceut, FIN-70211 Kuopio, Finland Procter & Gamble Pharmaceut, Hlth Care Res Ctr, Cincinnati, OH USA Procter& Gamble Pharmaceut Cincinnati OH USA es Ctr, Cincinnati, OH USA
Titolo Testata:
BONE
fascicolo: 4, volume: 29, anno: 2001,
pagine: 336 - 343
SICI:
8756-3282(200110)29:4<336:NBIAOC>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
RESORPTIVE BONE-DISEASE; IN-VITRO; OSTEOCLAST FORMATION; PHARMACOLOGICAL PROPERTIES; THERAPEUTIC EFFICACY; GASTRIC-ULCERS; ALENDRONATE; PAMIDRONATE; CLODRONATE; ACTIVATION;
Keywords:
bisphosphonate; apoptosis; Caco-2; mevalonate; prenylation; epithelium;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Rogers, MJ Univ Aberdeen, Sch Med, Dept Med & Therapeut, Polwarth Bldg, Aberdeen AB252ZD, Scotland Univ Aberdeen Polwarth Bldg Aberdeen Scotland AB25 2ZD cotland
Citazione:
S. Suri et al., "Nitrogen-containing bisphosphonates induce apoptosis of Caco-2 cells in vitro by inhibiting the mevalonate pathway: A model of bisphosphonate-inducedgastrointestinal toxicity", BONE, 29(4), 2001, pp. 336-343

Abstract

Bisphosphonates have become an important addition to the pharmacological armamentarium against postmenopausal osteoporosis. One of the major side effects of oral therapy with some nitrogen-containing bisphosphonates appears to be gastrointestinal (GI) intolerability, particularly esophageal irritation and ulceration. Because nitrogen-containing bisphosphonates can cause apoptosis in a variety of cell types in vitro, by inhibiting the mevalonate pathway, we hypothesized that the effect of these agents on the GI tract may be due to apoptosis or inhibition of growth of gut epithelial cells. A comparison between clodronate, etidronate, pamidronate, alendronate, and risedronate demonstrated that only the nitrogen-containing bisphosphonates wereeffective at inducing apoptosis or inhibiting proliferation of Caco-2 human epithelial cells in vitro, at concentrations of between 10 and 1000 mu mol/L. The ability of nitrogen-containing bisphosphonates to cause apoptosis and inhibit Caco-2 cell proliferation was due to inhibition of the mevalonate pathway, because the addition of farnesol, oxidized low-density lipoprotein (LDL) cholesterol, or especially geranylgeraniol suppressed the effects. Furthermore, pamidronate, alendronate, and risedronate inhibited protein prenylation in Caco-2 cells, as determined by analysis of the processing ofRap1A, a prenylated small GTPase. These studies suggest that the effects of nitrogen-containing bisphosphonates observed in the GI tract may be due to inhibition of proliferation or apoptosis of gut epithelial cells, following loss of prenylated proteins and sterols. (C) 2001 by Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 20:06:30