Sodium diethyldithiocarbamate, an AIDS progression inhibitor and a copper-binding compound, has proteasome-inhibitory and apoptosis-inducing activities in cancer cells.
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) alpha and ERbeta 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.
Pang
Haiyan
H
The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
Chen
Di
D
Cui
Qiuzhi Cindy
QC
Dou
Q Ping
QP
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D018450:Disease Progression; D004050:Ditiocarb / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D061988:Proteasome Inhibitors; D012996:Solutions
D061988:Proteasome Inhibitors; D012996:Solutions; D003300:Copper; D004050:Ditiocarb