Use of the disulfiram/copper complex for breast cancer chemoprevention in MMTV-erbB2 transgenic mice.
The disulfiram/copper complex (DS/Cu) has been demonstrated to exert potent anti-tumor effects in various types of cancer. At present, whether DS/Cu has chemopreventive effects on breast cancer development remains to be fully elucidated. In the present study, using MMTV-erbB2 transgenic mice, it was identified for the first time that DS/Cu treatment was able to inhibit cell growth in breast cancer cells while sparing normal cells in vitro, in addition to delaying the development of mammary tumor development in MMTV-erbB2 transgenic mice in vivo. Morphological examination demonstrated that DS/Cu treatment resulted in cell proliferation inhibition and apoptosis activation in vitro and in vivo. Furthermore, the present study observed that DS/Cu may inhibit proliferation via inhibition of AKT and cyclin D1 signaling and promote apoptosis via c-Jun N-terminal kinase activation and suppression of nuclear factor κB signaling. These results suggested that DS/Cu treatment may be a promising therapy for the prevention of erbB2-positive breast cancer.
Department of General Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
Yanhui
Y
Yang
Department of Pharmacy, The Central Hospital of Luoyang, Luoyang, Henan 471000, P.R. China.
Qian
Q
Deng
Department of Oncology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
Xiaoshan
X
Feng
Department of General Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
Junjun
J
Sun
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018890:Chemoprevention; D003300:Copper / Q000008:administration & dosage*; D019938:Cyclin D1; D004221:Disulfiram / Q000008:administration & dosage*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D051058:Oncogene Protein v-akt / Q000096:biosynthesis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects
D003300:Copper; D019938:Cyclin D1; D004221:Disulfiram; D051058:Oncogene Protein v-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; C530105:Ccnd1 protein, mouse; C524056:Erbb2 protein, mouse