l-Tryptophan Schiff base cadmium(II) complexes as a new class of proteasome inhibitors and apoptosis inducers in human breast cancer cells

Although cadmium is a widespread environmental contaminant and human carcinogen, our studies indicate an organic cadmium complex to be a potent inhibitor of proteasomal chymotrypsin-like (CT-like) activity, further capable of inducing apoptosis in a cancer cell-specific manner. Many clinical studies suggest the use of proteasome inhibitors as potential novel anticancer agents and in the present study, we have synthesized three novel l -tryptophan-containing cadmium complexes: Cd(C 17 H 15 N 4 O 2 ) 2 ·2CH 3 OH ( 1 ) (C 17 H 15 N 4 O 2   =   2-acetylpyrazine- l -tryptophan), Cd(C 17 H 15 N 2 O 3 ) 2 ·2CH 3 OH ( 2 ) (C 17 H 15 N 2 O 3   =   5-methylfurfural- l -tryptophan) and Cd(C 16 H 12 N 2 O 2 SBr) 2 ·2CH 3 OH ( 3 ) (C 16 H 12 N 2 O 2 SBr   =   5-bromo-2-thiophenecarbaldehyde- l -tryptophan) and found that under comparable conditions cadmium complexes 1 and 2 , but not 3 , have proteasome-inhibitory activity in human breast cancer MDA-MB-231 cells. Our results suggest that l -tryptophan Schiff base cadmium complexes are potent proteasome inhibitors.