Alendronate inhibits growth of high-grade chondrosarcoma cells.

Abstract

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.

• Authors: Michiro Susa, Takeshi Morii, Hiroo Yabe, Keisuke Horiuchi, Yoshiaki Toyama, Lawrence Weissbach, Francis J Hornicek, Hideo Morioka
• Journal: Anticancer research (Anticancer Res) Vol. 29 Issue 6 Pg. 1879-88 (Jun 2009) ISSN: 0250-7005 [Print] Greece
• PMID: 19528443 (Publication Type: Journal Article)

Chemical References

• Bone Density Conservation Agents
• Proteome
• Alendronate

Topics

• Alendronate (therapeutic use)
• Blotting, Western
• Bone Density Conservation Agents (therapeutic use)
• Bone Neoplasms (drug therapy, secondary)
• Cell Adhesion (drug effects)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Chondrosarcoma (drug therapy, pathology)
• Fluorescent Antibody Technique
• Humans
• Male
• Middle Aged
• Proteome (analysis)
• Tumor Cells, Cultured