Ni(II), Cu(II), and Zn(II) diethyldithiocarbamate complexes show various activities against the proteasome in breast cancer cells

Abstract

A series of three complexes with diethyldithiocarbamate ligand and three different metals (Ni, Cu, Zn) was prepared, confirmed by X-ray crystallography, and tested in human breast cancer MDA-MB-231 cells. Zinc and copper complexes, but not nickel complex, were found to be more active against cellular 26S proteasome than against purified 20S proteasome core particle. One of the possible explanations is inhibition of JAMM domain in the 19S proteasome lid.

Figures

Figure 1

Mechanism for inhibition of 20S proteasome by bortezomib and a suggested mechanism for metal-dithiocarbamate complexes to inhibit 26S proteasome in intact cells.

Figure 2

Probable analogy among published molecular mechanism of carboxypeptidase A domain inhibition by a zinc coordination particle and proposed inhibition of JAMM domain of 19S particle by zinc-diethyldithiocarbamate complex.