Disulfiram reduces metastatic osteosarcoma tumor burden in an immunocompetent Balb/c or-thotopic mouse model

Jared Anthony Crasto, Mitchell Stephen Fourman, Alejandro Morales Restrepo, Adel Mahjoub, Jonathan Brendan Mandell, Kavita Ramnath, Jessica C. Tebbets, Rebecca J. Watters, Kurt Richard Weiss

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Introduction: The overall survival rate of patients with osteosarcoma (OS) and pulmonary metastases has remained stagnant at 15-30% for several decades. Disulfiram (DSF) is an FDA-approved aldehyde dehydrogenase inhibitor that reduces the metastatic phenotype of OS cells in vitro. Here we evaluate its in vivo efficacy, as compared to doxorubicin chemotherapy, in a previously-validated orthotopic model of metastatic OS. Results: All treatment groups displayed a significantly reduced quantitative OS metastatic burden compared with controls. The metastatic burden of Lo DSF-treated animals was equivalent to the DXR group. Ninety-five percent of control animals displayed evidence of metastatic disease, which was significantly greater than all treatment groups. Discussion: Disulfiram treatment resulted in a reduced burden of OS metastatic disease compared with controls. This was statistically-equivalent to doxorubicin. No additive effect was observed between these two therapies. Materials and Methods: One-hundred twenty immunocompetent Balb/c mice received proximal tibia paraphyseal injections of 5 × 105 K7M2 murine OS cells. Therapy began three weeks after injection: saline (control), low-dose disulfiram (Lo DSF), high-dose disulfiram (Hi DSF), doxorubicin (DXR), Lo DSF + DXR, and Hi DSF + DXR. Transfemoral amputations were performed at 4 weeks. Quantitative metastatic tumor burden was measured using near-infrared indocyanine green (ICG) angiography.

Original languageEnglish (US)
Pages (from-to)30163-30172
Number of pages10
Issue number53
StatePublished - Jul 10 2018
Externally publishedYes


  • Akt
  • Aldehyde dehydrogenase
  • Bad
  • Disulfiram
  • Osteosarcoma

ASJC Scopus subject areas

  • Oncology


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