A new synthetic Cu(II) compound, [Cu3(p-3-bmb)2Cl4·(CH3OH)2]n, inhibits tumor growth in vivo and in vitro

• Published in: European journal of pharmacology 2014-02, Vol.724, p.77-85
• Main Authors: Li, Ruili, Cui, Binglin, Li, Yuwen, Zhao, Chao, Jia, Na, Wang, Chao, Wu, Yin, Wen, Aidong
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antitumor; Apoptosis; Apoptosis - drug effects; Cell Cycle; Cell Cycle - drug effects; Cell Line, Tumor; Coordination Complexes - pharmacology; Coordination Complexes - therapeutic use; Cu(II) compound; HeLa Cells; Humans; Intracellular Signaling Peptides and Proteins - metabolism; Male; Membrane Potential, Mitochondrial - drug effects; Mice; Mice, Inbred ICR; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Tumor Burden - drug effects
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2013.12.007

Copper(II) mixed-ligand complex, [Cu3(p-3-bmb)2Cl4 (CH3OH)2]n (Cu(II) compound), where p-3-bmb=1((2-(pyridine-3-yl)-1H-benzoimidazol-1-yl) methyl)-1Hbenzotriazole, has been recently found to possess potent anti-tumor activities both in vivo and in vitro. In this study, we demonstrated that Cu(II) compound significantly inhibited tumor growth in mice that inoculated with S180 cells. Meanwhile, the viabilities of HeLa and SGC-7901 cells were inhibited by Cu(II) compound with IC50 values in the range of 5–30μM. Further mechanistic studies revealed that Cu(II) compound treatment induced cell cycle arrested at G1 phase through p53, p21, cyclinD1, cdk4, pRb and E2F1. Cu(II) compound treatment also induced apoptosis of HeLa and SGC-7901 cells which were accompanied with decrease in mitochondrial membrane potential, increase in reactive oxygen species production, release of cytochrome C, cleavage of caspase-9, caspase-3 and poly ADP-ribose polymerase (PARP) as well as activations of bcl-2 and bax. These results indicate that Cu(II) compound has a promising potential to become a novel anti-cancer agent. [Display omitted]