title: A new synthetic Cu(II) compound, [Cu3(p-3-bmb)2Cl4·(CH3OH)2]n, inhibits tumor growth in vivo and in vitro.
abstract: 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 5-30 μM. 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.
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Changle West Street 15, Xi'an, Shaanxi 710032, China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Zhengzhou University, Kexue Street 100, Zhengzhou, Henan 450001, China.
authors.forename: Binglin
authors.initials: B
authors.lastname: Cui
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Changle West Street 15, Xi'an, Shaanxi 710032, China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Changle West Street 15, Xi'an, Shaanxi 710032, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Changle West Street 15, Xi'an, Shaanxi 710032, China.
authors.forename: Na
authors.initials: N
authors.lastname: Jia
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Changle West Street 15, Xi'an, Shaanxi 710032, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Changle West Street 15, Xi'an, Shaanxi 710032, China. Electronic address: wuyin_2005@126.com.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Changle West Street 15, Xi'an, Shaanxi 710032, China. Electronic address: lwrcll@163.com.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000494:pharmacology / Q000627:therapeutic use*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species
keywords: Antitumor; Apoptosis; Cell Cycle; Cu(II) compound; Reactive oxygen species