title: The bisphosphonates alendronate and zoledronate are inhibitors of canine and human osteosarcoma cell growth in vitro.
abstract: Bisphosphonates (BPs) are a class of non-hydrolysable analogues of pyrophosphate that have high affinity for bone mineral and are inhibitors of bone resorption. The in vitro effects of two nitrogen-containing BPs, alendronate (ALE) and zoledronate (ZOL), on growth, induction of apoptosis and effects on cell-cycle distribution in two canine and two human osteosarcoma (OSA) cell lines are investigated here. Both significantly (P < 0.001) reduced cell growth in all cell lines, as assessed by a colorimetric assay with IC(50) values in the range of 7.3-61.4 microM and 7.9-36.3 microM for ALE and ZOL, respectively. Both BPs caused a significant (P < 0.001) dose-dependent increase in the proportion of cells undergoing apoptosis, as assessed both by cell-cycle analysis and by annexin-V binding. Both ALE and ZOL altered the proportion of cells in each phase of the cell cycle, but the extent and proportion was both drug and cell line dependent. These data indicate that the nitrogen-containing BPs have direct anti-tumour activity against canine and human OSA cells.
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: V J
authors.initials: VJ
authors.lastname: Poirier
authors.forename: M K
authors.initials: MK
authors.lastname: Huelsmeyer
authors.forename: I D
authors.initials: ID
authors.lastname: Kurzman
authors.forename: D H
authors.initials: DH
authors.lastname: Thamm
authors.forename: D M
authors.initials: DM
authors.lastname: Vail