Minnelide reduces tumor burden in preclinical models of osteosarcoma

Cancer Lett. 2013 Jul 28;335(2):412-20. doi: 10.1016/j.canlet.2013.02.050. Epub 2013 Mar 14.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antineoplastic Agents, Alkylating
  • BIRC5 protein, human
  • Diterpenes
  • Epoxy Compounds
  • Heat-Shock Proteins
  • Inhibitor of Apoptosis Proteins
  • MYC protein, human
  • NF-kappa B
  • Organophosphates
  • Phenanthrenes
  • Proto-Oncogene Proteins c-myc
  • Survivin
  • triptolide
  • 14-O-phosphonooxymethyltriptolide
  • Caspase 3
  • Caspase 7
  • Caspase 9