title: Nanoscaled carborane ruthenium(II)-arene complex inducing lung cancer cells apoptosis.
abstract: BACKGROUND
  The new ruthenium(II)-arene complex, which bearing a carborane unit, ruthenium and ferrocenyl functional groups, has a novel versatile synthetic chemistry and unique properties of the respective material at the nanoscale level. The ruthenium(II)-arene complex shows significant cytotoxicity to cancer cells and tumor-inhibiting properties. However, ruthenium(II)-arene complex of mechanism of anticancer activity are scarcely explored. Therefore, it is necessary to explore ruthenium(II)-arene complex mechanism of anticancer activity for application in this area.
  
  
  RESULTS
  In this study, the ruthenium(II)-arene complex could significantly induce apoptosis in human lung cancer HCC827 cell line. At the concentration range of 5 μM-100 μM, ruthenium(II)-arene complex had obvious cell cytotoxicity effect on HCC827 cells with IC(50) values ranging 19.6 ± 5.3 μM. Additionally, our observations demonstrate that the ruthenium(II)-arene complex can readily induce apoptosis in HCC827 cells, as evidenced by Annexin-V-FITC, nuclear fragmentation as well as DNA fragmentation. Treatment of HCC827 cells with the ruthenium(II)-arene complex resulted in dose-dependent cell apoptosis as indicated by high cleaved Caspase-8,9 ratio. Besides ruthenium(II)-arene complex caused a rapid induction of cleaved Caspase-3 activity and stimulated proteolytic cleavage of poly-(ADP-ribose) polymerase (PARP) in vitro and in vivo.
  
  
  CONCLUSIONS
  In this study, the ruthenium(II)-arene complex could significantly induce apoptosis in human lung cancer HCC827 cell line. Treatment of HCC827 cells with the ruthenium(II)-arene complex resulted in dose-dependent cell apoptosis as indicated by high cleaved Caspase-8,9 ratio. Besides ruthenium(II)-arene complex caused a rapid induction of cleaved Caspase-3 activity and stimulated proteolytic cleavage of poly-(ADP-ribose) polymerase (PARP) in vitro and in vivo. Our results suggest that ruthenium(II)-arene complex could be a candidate for further evaluation as a chemotherapeutic agent for human cancers, especially lung cancer.
authors.affiliation: State Key Lab of Bioelectronics (Chien-Shiung Wu Lab), Department of Biological Science and Medical Engineering Southeast University, Nanjing, 210096, PR China.
authors.forename: Gen
authors.initials: G
authors.lastname: Zhang
authors.forename: Chunhui
authors.initials: C
authors.lastname: Wu
authors.forename: Hongde
authors.initials: H
authors.lastname: Ye
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D001880:Boranes / Q000008:administration & dosage* / Q000737:chemistry; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures / Q000008:administration & dosage*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017975:Ruthenium Compounds / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D001880:Boranes; D017975:Ruthenium Compounds; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases