Possible Interaction: Copper and Clioquinol

“Here we show that increased intracellular levels of copper , using the ionophore clioquinol , leads to a potent inhibition of NFκB pathways, induced by multiple distinct stimuli.”

“We report here that after binding to copper, clioquinol can inhibit the proteasomal chymotrypsin-like activity, repress androgen receptor (AR) protein expression, and induce apoptotic cell death in human prostate cancer LNCaP and C4-2B cells.”

“This finding suggests that clioquinol can act therapeutically by changing the distribution of copper or facilitating copper uptake rather than by decreasing copper levels.”

“Using a yeast model system, we show that adding clioquinol to the yeast culture medium drastically increased the intracellular copper concentration but there was no significant effect observed on zinc levels.”

“The concentrations of copper and zinc in the brain rose by about 15% in mice treated with clioquinol.”

“On the other hand, clioquinol (20–50 µM) significantly increased the cellular level of copper within 24 h. Clioquinol (50 µM) induced the oxidation of the copper chaperone antioxidant 1 (ATOX1), suggesting its inactivation and inhibition of copper transport.”

“We have previously reported that when mixed with copper , 8-hydroxyquinoline (8-OHQ) and its analog clioquinol ( CQ ) inhibited the proteasomal activity and proliferation in cultured human cancer cells.”

“Our findings indicate that CQ can interact with cellular Cu in vivo, dysregulates the Cu/Zn balance and is able to convert Cu(I) to Cu(II) in tumor tissue.”

“The exposure of Cu + CQ led to a modest but significant increase in cerebral Cu levels, most likely due to an enhanced transport of CQ–Cu complexes.”

“Moreover, treatment of cells with copper in the presence of CQ or B2Q resulted in copper accumulation in the nuclei, while PBT2-guided copper was distributed near to the cell membrane.”