Disulfiram

Disulfiram-copper complex potently inhibits the proteasomal activity in cultured breast cancer MDA-MB-231 and MCF10DCIS.com cells, but not normal, immortalized MCF-10A cells, before induction of apoptotic cancer cell death. ^[1]

Disulfiram (DS), a clinically used anti-alcoholism drug, strongly inhibits constitutive and 5-FU-induced NF-kappaB activity in a dose-dependent manner. Disulfiram inhibits both NF-kappaB nuclear translocation and DNA binding activity but has no effect on 5-FU-induced IkappaBalpha degradation. Disulfiram significantly enhances the apoptotic effect of 5-FU on DLD-1 and RKO(WT) cell lines and synergistically potentiated the cytotoxicity of 5-FU to both cell lines. Disulfiram also effectively abolishes 5-FU chemoresistance in a 5-FU resistant cell line H630(5-FU) in vitro. ^[2]

Oseltamivir decreases the number of viable cells, and the addition of CuCl(2) significantly enhances the DSF-induced cell death to less than 10% of control. ^[3]

Disulfiram given to melanoma cells in combination with Cu2+ or Zn2+ decreases expression of cyclin A and reduces proliferation in vitro at lower concentrations than disulfiram alone. ^[4]

Disulfiram significantly inhibits the tumor growth (by 74%), associated with in vivo proteasome inhibition (as measured by decreased levels of tumor tissue proteasome activity and accumulation of ubiquitinated proteins and natural proteasome substrates p27 and Bax) and apoptosis induction (as shown by caspase activation and apoptotic nuclei formation) in mice bearing MDA-MB-231 tumor xenografts. ^[1]

Disulfiram blocks the P-glycoprotein extrusion pump, inhibits the transcription factor nuclear factor-kappaB, sensitizes tumors to chemotherapy, reduces angiogenesis, and inhibits tumor growth in mice. Disulfiram inhibits growth and angiogenesis in melanomas transplanted in severe combined immunodeficient mice, and these effects are potentiated by Zn2+ supplementation. ^[4]

• Cell lines

  MDA-MB-231 cells

• Concentrations

  20 μM

• Incubation Time

  24 h

• Method

  Cells cultured in medium containing 25 µM copper for 3 days and then maintained in normal growth medium (without additional copper) were treated with 20 µM DSF or TM or vehicle DMSO for 24 hours.