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-κB pathway.
Bibliographical noteFunding Information:
This study was supported by grants R01CA124723 and R01CA170496 from the NIH (A.K.S.), by a Faculty Research and Development grant from the University of Minnesota Academic Health Center, by a translational research grant from the Masonic Cancer Center, University of Minnesota, by grants from the Wyckoff Rein in Sarcoma (S.S.).
- Heat shock proteins