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

biomed - Wang , Zhang Gen , Wu Chunhui , Ye Hongde , Yanhong , Wang Xuemei

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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 . Conclusion 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.

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Publié par	biomed
Publié le	01 janvier 2011
Nombre de lectures	9
Langue	English

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Zhanget al.Journal of Nanobiotechnology2011,9:6 http://www.jnanobiotechnology.com/content/9/1/6

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Open Access

Nanoscaled carborane ruthenium(II)arene complex inducing lung cancer cells apoptosis 1 1 2 2 1* Gen Zhang , Chunhui Wu , Hongde Ye , Hong Yan , Xuemei Wang

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 5μM100μM, ruthenium(II)arene complex had obvious cell cytotoxicity effect on HCC827 cells with IC50values ranging 19.6 ± 5.3μM. 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 vitroandin vivo. Conclusion: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 vitroandin 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.

Background Enormous interest has been focused on the research of metallopharmaceuticals in order to find good alterna tives to platinum drugs because of their significant clini cal side effects and resistance that cause relapse of cisplatin [1]. In recent years, ruthenium complexes have attracted much interest because they exert their tumor inhibiting effects by a mode of action different from that of Pt compounds [2]. Furthermore, they show a favor able toxicity profile in clinical trials: in the case of the rutheniumindazole complex KP1019 only very

* Correspondence: xuewang@seu.edu.cn 1 State Key Lab of Bioelectronics (ChienShiung Wu Lab), Department of Biological Science and Medical Engineering Southeast University, Nanjing, 210096, PR China Full list of author information is available at the end of the article

moderate toxicities were observed in a dose range in which proteins were on average loaded with one ruthe nium species, which should be sufficient for therapeutic activity [3]. Recently, potential bioactive moieties, such as carbor ane and ferrocene (Fc), have been extensively involved in newtype drug design because of their unique proper ties. Carboranes are carboncontaining polyhedral boroncluster compounds with globular geometry. Novel carborane derivatives were synthesized to clarify its anti cancer activity [4]. A myriad of compounds containing single or multiplecarborane clusters were synthesized and evaluated in both cellular and animal studies [5]. Carboranes are a class of carboncontaining polyhedral boroncluster compounds with remarkable thermal sta bility and exceptional hydrophobicity [6]. Carboranes

© 2011 Zhang et al; licensee 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.

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

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