Alendronate inhibits growth of high-grade chondrosarcoma cells.
BACKGROUND
Conventional chemotherapy is ineffective for high-grade chondrosarcomas, highlighting the need for improved chemotherapies. Various clinical trials have been initiated using antiapoptotic agents and perifosine, and are truly in the experimental phases. Chondrosarcoma is still therefore considered a surgical disease despite its aggressive features of recurring locally and spreading to the lungs. Bisphosphonates inhibit growth of various cell types, including cancer cells and perhaps chondrosarcoma.


METHODS
The effect of different concentrations of alendronate on cell proliferation, migration, apoptosis and cytoskeleton reorganization as well as on the regulation of intracellular protein expression were analyzed for the high-grade chondrosarcoma cell line CS-1. Mevalonate pathway intermediates were used in some experiments to assess mechanistic aspects.


RESULTS
Alendronate decreased cell viability of CS-1 by inhibiting cell proliferation and cell migration. Alendronate-induced loss of cell viability led to a sequence of events including apoptosis and cytoskeletal rearrangements. Moreover, changes in the expression levels of various proteins involved in cell proliferation, migration, cell cycle, apoptosis and cytoskeleton reorganization were demonstrated.


CONCLUSIONS
Alendronate exerts antiproliferative effects by perturbing various signaling pathways in CS-1 cells. These findings may lead to new treatment options for high-grade chondrosarcoma.
Susa
Michiro
M
Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan. msusa@partners.org
Morii
Takeshi
T
Yabe
Hiroo
H
Horiuchi
Keisuke
K
Toyama
Yoshiaki
Y
Weissbach
Lawrence
L
Hornicek
Francis J
FJ
Morioka
Hideo
H
D019386:Alendronate / Q000627:therapeutic use*; D015153:Blotting, Western; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002813:Chondrosarcoma / Q000188:drug therapy* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000032:analysis; D014407:Tumor Cells, Cultured
D050071:Bone Density Conservation Agents; D020543:Proteome; D019386:Alendronate