Sodium diethyldithiocarbamate, an AIDS progression inhibitor and a copper-binding compound, has proteasome-inhibitory and apoptosis-inducing activities in cancer cells

Abstract

Diethyldithiocarbamate (DDTC) is a member of the dithiocarbamate family and a potent copper-chelating agent. DDTC was used in a clinical trial for patients with HIV-1 infection and showed a significant delay in progression to AIDS. In this study, we investigated the effects of DDTC-copper complex in human prostate and breast cancer cells. We found that DDTC was capable of binding copper and forming a new complex that potently inhibited the proteasomal chemotrypsin-like activity, decreased expression of androgen receptor (AR), estrogen receptor (ER) α and ERβ proteins, and induced apoptosis in both prostate and breast cancer cells. Our data support the concept of using accumulated copper in cancer cells and tissues as a novel target for chemotherapy. This study provides a mechanistic interpretation for utilization of copper chelators in cancer treatment.