14-o-phosphonooxymethyltriptolide and Osteosarcoma

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.

Topics: Animals; Antineoplastic Agents, Alkylating; Apoptosis; Caspase 3; Caspase 7; Caspase 9; Cell Line, Tumor; Cell Survival; Diterpenes; Down-Regulation; Epoxy Compounds; Female; Gene Expression Regulation, Neoplastic; Heat-Shock Proteins; Humans; Inhibitor of Apoptosis Proteins; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation; NF-kappa B; Organophosphates; Osteoblasts; Osteosarcoma; Phenanthrenes; Proto-Oncogene Proteins c-myc; Survivin; Tumor Burden; Xenograft Model Antitumor Assays