Journal
CANCER LETTERS
Volume 335, Issue 2, Pages 412-420Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2013.02.050
Keywords
Triptolide; Minnelide; Osteosarcoma; Heat shock proteins; NF-kappa B
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Funding
- NIH [R01CA124723, R01CA170496]
- University of Minnesota Academic Health Center
- Masonic Cancer Center, University of Minnesota
- Wyckoff Rein in Sarcoma
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Osteosarcoma is the most common bone cancer in children and adolescents with a 5-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on osteosarcoma. Triptolide was effective in significantly inducing apoptosis in all osteosarcoma cell lines tested but had no significant effect on the human osteoblast cells. Notably, Minnelide treatment significantly reduced tumor burden and lung metastasis in the orthotopic and lung colonization models. Triptolide/Minnelide effectively downregulated the levels of pro-survival proteins such as heat shock proteins, cMYC, survivin and targets the NF-kappa B pathway. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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