Clioquinol Independently Targets NF-κB and Lysosome Pathways in Human Cancer Cells

We have reported that clioquinol alters lysosome integrity, inhibits nuclear factor kappa B (NF-kappa B) activity, and induces apoptosis in human cancer cells. The present study investigated whether clioquinol targets both pathways dependently or independently in human prostate cancer DU 145 cells. Clioquinol inhibited NF-kappa B activity, an effect being more pronounced in the presence of zinc. This inhibition was mediated through a reduced nuclear level of p65, the most frequently detected NF-kappa B subunit. Clioquinol also induced alterations of lysosome permeability in a zinc concentration-dependent manner. Pretreatment of the cells with ammonium, a lysosome protection agent, attenuated clioquinol-induced disruption of the lysosomes, yet ammonium had no effect on clioquinol-induced inhibition of NF-kappa B signaling. MG132, an established NF-kappa B inhibitor, suppressed NF-kappa B activity without causing alterations of lysosome permeability. These findings indicate that clioquinol targets NF-kappa B and lysosome pathways independently, favoring further development of clioquinol as a novel anticancer agent.