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Disulfiram

CAS No. : 97-77-8

MCE 国际站：Disulfiram

产品活性：Disulfiram (Tetraethylthiuram disulfide) 是特异性的乙醛脱氢酶 1 型 (ALDH1) 抑制剂，对酒精具有急性敏感性。Disulfiram 有效抑制人体和小鼠细胞中脂质体中的 GSDMD 孔形成，炎性体介导的细胞凋亡和 IL-1β 分泌。双硫仑 + Cu²⁺ 可增加细胞内 ROS 水平，引发卵巢癌干细胞凋亡。

研究领域：Metabolic Enzyme/Protease  |  Immunology/Inflammation  |  Apoptosis

作用靶点：Aldehyde Dehydrogenase (ALDH)  |  Interleukin Related  |  Pyroptosis  |  Apoptosis

In Vitro: 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. 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.?Oseltamivir decreases the number of viable cells, and the addition of CuCl₂ significantly enhances the DSF-induced cell death to less than 10% of control.?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.
?Disulfiram (0.1 nM-10 μM; 72 h)?+?Cu²⁺ combination enhances the cytotoxicity on ovarian cancer cell lines.

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

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