Inhibition of osteosarcoma cell proliferation by the Hedgehog-inhibitor cyclopamine.
Osteosarcomas (OS) are the most frequent primary malignant bone tumors in humans. Even though OS are chemosensitive, about 30% of patients must be considered poor responders and consequently have a dismal long term prognosis. The Hedgehog (Hh) gene is crucial in the signalling pathways of proliferation and differentiation during embryonic development. There is evidence that uncontrolled activation of this pathway results in specific types of cancer and that inhibition of Hh signalling is able to suppress tumour growth and to induce apoptosis of neoplastic cells. This study investigates the impact of the steroidal alkaloid and Hh-inhibitor cyclopamine on osteosarcoma cells. Thus we demonstrate the drug's impact on cellular proliferation, cell cycle cell death as well as the cells' metabolism. We here demonstrate that cyclopamine exhibits a high efficacy against the osteosarcoma cell lines HOS, SaOS and OS-KA, a self-established primary osteosarcoma cell line. In particular, cyclopamine is able to inhibit proliferation and to promote cell death. Our results provide evidence for the potency of the Hh-inhibitor cyclopamine as a future treatment of osteosarcomas.
Warzecha
J
J
Department of Orthopedic Surgery, Johann Wolfgang Goethe-University Hospital, Frankfurt am Main, Germany. j.warzecha@friedrichsheim.de
Göttig
S
S
Chow
K U
KU
Brüning
C
C
Percic
D
D
Boehrer
S
S
Brude
E
E
Kurth
A
A
D000970:Antineoplastic Agents; D001859:Bone Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D053823:Hedgehog Proteins / Q000187:drug effects*; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014704:Veratrum Alkaloids
D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D014704:Veratrum Alkaloids; C000541:cyclopamine