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Alendronate inhibits growth of high-grade chondrosarcoma cells
Michiro Susa1, Takeshi Morii, Hiroo Yabe
1Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan. msusa@partners.org
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.
Materials And 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.
Conclusion:
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.
