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

Jared Anthony Crasto1, Mitchell Stephen Fourman1, Alejandro Morales-Restrepo1

  • 1Musculoskeletal Oncology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

Oncotarget
|July 27, 2018
PubMed
Abstract

Insights

Disulfiram significantly reduced osteosarcoma metastasis in mice, matching doxorubicin efficacy. Combining disulfiram with doxorubicin did not improve outcomes compared to doxorubicin alone.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Metastasis Research

Background:

  • Osteosarcoma (OS) with pulmonary metastases has a poor survival rate (15-30%).
  • Disulfiram (DSF), an aldehyde dehydrogenase inhibitor, shows in vitro efficacy against OS metastasis.
  • Current treatments for metastatic OS have limited success.

Purpose of the Study:

  • To evaluate the in vivo efficacy of disulfiram (DSF) in reducing osteosarcoma (OS) metastasis.
  • To compare DSF's efficacy against doxorubicin (DXR) chemotherapy in a validated orthotopic OS model.
  • To assess the potential additive effect of combining DSF and DXR.

Main Methods:

  • 120 immunocompetent mice received K7M2 murine OS cells.
  • Treatments included saline, low-dose DSF, high-dose DSF, DXR, and combinations.
  • Metastatic tumor burden was quantified using near-infrared indocyanine green (ICG) angiography.

Main Results:

  • All treatment groups showed significantly reduced OS metastatic burden compared to controls.
  • Low-dose DSF treatment was equivalent in efficacy to doxorubicin (DXR).
  • 95% of control animals had metastatic disease, significantly higher than all treatment groups.

Conclusions:

  • Disulfiram treatment effectively reduced osteosarcoma metastatic burden in vivo.
  • DSF demonstrated comparable efficacy to doxorubicin in this model.
  • No additive therapeutic benefit was observed when combining disulfiram and doxorubicin.

Related Concept Videos

Development of Immunocompetence01:22

Development of Immunocompetence

The initiation of cell-mediated immunity can be observed as early as the third month of fetal growth, with active antibody-mediated immunity following approximately one month later.
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
927
Reducing Line Loss01:18

Reducing Line Loss

In a three-phase circuit, line loss is an indicator of energy dissipated as heat due to the resistance of transmission lines. To address this, incorporating transformers into the system—a step-up transformer at the source and a step-down transformer at the load—is a strategic solution. Two three-phase transformers are introduced to improve this.
With a step-up transformer at the source, the voltage is increased, thereby reducing the current in the transmission lines since power loss in...
390
Methods of reducing fever01:22

Methods of reducing fever

The signs and symptoms of fever include hot and dry skin, flushed face, thirst, muscle aches, anorexia, headache, tachycardia, tachypnea, and fatigue. Elevated body temperature is reduced using two methods: pharmacological and nonpharmacological. Proper identification and treatment of the root cause of a fever is of utmost importance.
Pharmacological Methods of Reducing Fever:
1.4K
Adaptations that Reduce Water Loss01:57

Adaptations that Reduce Water Loss

Though evaporation from plant leaves drives transpiration, it also results in loss of water. Because water is critical for photosynthetic reactions and other cellular processes, evolutionary pressures on plants in different environments have driven the acquisition of adaptations that reduce water loss.
28.2K
Role of Reduced Coenzymes NADH and FADH₂01:29

Role of Reduced Coenzymes NADH and FADH₂

The energy released from the breakdown of the chemical bonds within nutrients can be stored either through the reduction of electron carriers or in the bonds of adenosine triphosphate (ATP). In living systems, a small class of compounds functions as mobile electron carriers, molecules that bind to and shuttle high-energy electrons between compounds in pathways. The principal electron carriers that will be considered originate from the B vitamin group and are derivatives of nucleotides; they are...
16.9K
Redox Titration: Other Oxidizing and Reducing Agents01:26

Redox Titration: Other Oxidizing and Reducing Agents

Besides iodine, other oxidizing or reducing agents can serve as titrants in redox titrations. Common oxidizing titrants include KMnO4, cerium(IV), and K2Cr2O7. The choice of oxidizing titrants depends on factors like stability, cost, analyte strength, and reaction rate between the analyte and titrant. KMnO4 is a strong oxidizing titrant that reduces from Mn(VII) to Mn(II) in a highly acidic solution, simultaneously oxidizing the analyte to a higher oxidation state. In this case, KMnO4 acts as a...
1.4K