Figure 2.
Anticancer mechanisms of DSF. DSF combined with Cu or Cu(DDC)2 inhibits proteasome activity via NPL4 aggregation, leading to reduced NF-κB and NRF2 activity and consequently apoptosis. Furthermore, DSF, DSF/Cu, and Cu(DDC)2 induce ROS production and inhibit ALDH activity to inhibit ROS scavenging, then initiating DNA damage, cell cycle arrest, and caspase pathway-mediated apoptosis. ALDH: Aldehyde dehydrogenase; Cu(DDC)2: Bis-diethyldithiocarbamate-copper; CTR1: Copper-transport-related protein; DDC: Diethyldithiocarbamate; DSF: Disulfiram; ER: Edoplasmic reticulum; JNK: c-Jun N-terminal kinase; MAPK: Mitogen-activated protein kinase; NF-κB: Nuclear factor-kappa B; NPL4: Nuclear protein localization protein 4; NRF2: Nuclear factor erythroid 2-related factor 2; P-gp: P-glycoprotein; ROS: Reactive oxygen species; Ub: Ubiquitination.