Clioquinol independently targets NF-kappaB and lysosome pathways in human cancer cells

We have reported that clioquinol alters lysosome integrity, inhibits nuclear factor kappa B (NF-kappaB) 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-kappaB 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-kappaB 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-kappaB signaling. MG132, an established NF-kappaB inhibitor, suppressed NF-kappaB activity without causing alterations of lysosome permeability. These findings indicate that clioquinol targets NF-kappaB and lysosome pathways independently, favoring further development of clioquinol as a novel anticancer agent.