Seminars Archive

Copper Spatial Distribution, Concentration and Status in Normal and Tumor Tissues: Significance in Cancer Prevention and Treatment

Abstract
The rapid growing results of studies suggest that copper (Cu) is a novel, selective target for cancer therapies. It has been shown that Cu is essential for tumor angiogenesis and high levels of Cu are found in many types of human cancers compared with normal tissues. Recent research also suggests the use of proteasome inhibitors as potential novel anticancer drugs. Most recently we found that the anti-Alzheimer\'s disease drug Clioquinol (CQ), a Cu-binding compound,is able to target the elevated tumor cellular Cu to form a potent proteasome inhibitor and apoptosis inducer in cultured human cancer cells and in mice bearing xenografts of human tumors. We report here elemental mapping measurements in normal and human prostate tumor xenograft tissues collected from mice. The spatial distributions were measured using the BioCAT x-ray microprobe. A set of KB mirrors, a SDD large area Ketek detector comprises the microprobe setup. Consistent with the literature, we found increased Cu concentration in prostate tumor tissues compared to the normal tissues. Most significantly, prostate tumors treated with CQ contained 3-6-fold higher level of Cu than the control tumors. This result clearly demonstrates the ability of CQ to interact with Cu in blood and subsequently bring the proteasome-inhibitory Cu complex into tumors, which is responsible for the observed Cu concentration increase in tumor tissues and the anti-tumor activities. Other important differences of the Ca, Fe, K and Zn elemental distributions were also found. This is another indication of additional interconnection between the CQ complex, the cellular Cu and the other.