Metal-based 2,3-indolinedione derivatives as proteasome inhibitors and inducers of apoptosis in human cancer cells.

摘要: Proliferation and apoptotic pathways are tightly regulated in cells by the ubiquitin-proteasome system (UPS). Alterations UPS may result cellular transformation or other pathological conditions. The proteasome is indeed often found to be overactive cancer cells. It has been reported that 2,3-indolinedione (L), which exists marine organisms, as well mammals, a inhibitor. Studies have shown metal-based complexes inhibit activity induce apoptosis certain human In current study, we synthesized six novel with derivatives of 2,3-indolinedione: [Cd (C15H11O3N2) (CH3COO)] (C1), (C15H11O2N2) (C2), [Co (C15H9O4N2) (C3), (C4), [Zn (C19H14O3N3) (C5) (C17H13O3N2) (C6). We sought characterize assess inhibitory anti-proliferative effects these breast (MDA-MB-231) prostate (LNCaP PC-3) cells, order determine whether specific structures contribute inhibition tumor induction apoptosis. results revealed complexes, C1, C3 C5, but not their counterparts, C2, C4 C6, inhibited chymotrypsin-like 26S proteasome; addition, promoted accumulation target protein, Bax, cell growth induced concentration- time-dependent manner due unique structures. Our data suggest study including aromatic ring electron-attracting groups, an interesting research direction for development anticancer drugs.