Nanoscaled carborane ruthenium(II)-arene complex inducing lung cancer cells apoptosis

Journal of Nanobiotechnology

Research

Gen Zhang¹  Xuemei Wang¹  Chunhui Wu¹  Hongde Ye²  Hong Yan² 

[1] Department of Biological Science and Medical Engineering Southeast University, State Key Lab of Bioelectronics (Chien-Shiung Wu Lab), 210096, Nanjing, PR China;State Key Lab of Coordination Chemistry, School of Chemistry and Chemical Engineering, The Joint Laboratory of Metal Chemistry, Nanjing University, 210093, Nanjing, Jiangsu, PR China;

关键词: Ruthenium;    HCC827 Cell;    Boron Neutron Capture Therapy;    Arene Complex;    Induce Cancer Cell Apoptosis;   

DOI  :  10.1186/1477-3155-9-6

 received in 2010-11-25, accepted in 2011-02-22,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsIn 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 IC50 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.ConclusionIn 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.

【 授权许可】

Unknown   
© Zhang et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.