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Title: | Role of SIRT1-mediated mitochondrial and Akt pathways in glioblastoma cell death induced by cotinus coggygria flavonoid nanoliposomes | Authors: | Wang, G Wang, JJ To, TSS Zhao, HF Wang, J |
Issue Date: | 2015 | Source: | International journal of nanomedicine, 2015, v. 10, p. 5005-5023 | Abstract: | Flavonoids, the major polyphenol components in Cotinus coggygria (CC), have been found to show an anticancer effect in our previous study; however, the exact mechanisms of inducing human glioblastoma (GBM) cell death remain to be resolved. In this study, a novel polyvinylpyrrolidone K-30/sodium dodecyl sulfate and polyethyleneglycol-coated liposome loaded with CC flavonoids (CCFs) was developed to enhance solubility and the antibrain tumor effect, and the molecular mechanism regarding how CCF nanoliposomes (CCF-NLs) induce apoptotic cell death in vitro was investigated. DBTRG-05MG GBM cell lines treated with CCF-NLs showed potential antiproliferative effects. Regarding the underlying mechanisms of inducing apoptosis in DBTRG-05MG GBM cells, CCF-NLs were shown to downregulate the expression of antiapoptotic B-cell lymphoma/leukemia 2 (Bcl-2), an apoptosis-related protein family member, but the expression of proapoptotic Bcl-2-associated X protein was enhanced compared with that in controls. CCF-NLs also inhibited the activity of caspase-3 and -9, which is the initiator caspase of the extrinsic and intrinsic apoptotic pathways. Blockade of caspase activation consistently induced apoptosis and inhibited growth in CCF-NL-treated DBTRG-05MG cells. This study further investigated the role of the Akt pathway in the apoptotic cell death by CCF-NLs, showing that CCF-NLs deactivated Akt. Specifically, CCF-NLs downregulated the expression of p-Akt and SIRT1 as well as the level of phosphorylated p53. Together, these results indicated SIRT1/p53-mediated cell death was induced by CCF-NLs, but not by extracellular signal-regulated kinase, in DBTRG-05MG cells. Overall, this study suggested caspase-dependent activation of both the intrinsic and extrinsic signaling pathways, probably through blockade of the SIRT1/p53-mediated mitochondrial and Akt pathways to exert the proapoptotic effect of CCF-NLs in DBTRG-05MG GBM cells. | Keywords: | Cell death Cotinus coggygria flavonoid nanoliposomes Mitochondrial PI3K/Akt pathway SIRT1 |
Publisher: | Dove Medical Press | Journal: | International journal of nanomedicine | ISSN: | 1176-9114 | EISSN: | 1178-2013 | DOI: | 10.2147/IJN.S82282 | Rights: | © 2015 Wang et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). The following publication: Wang, G., Wang, J. J., To, T. S., Zhao, H. F., & Wang, J. (2015). Role of SIRT1-mediated mitochondrial and Akt pathways in glioblastoma cell death induced by Cotinus coggygria flavonoid nanoliposomes. International journal of nanomedicine, 10, 5005-23 is available at http://dx.doi.org/10.2147/IJN.S82282 |
Appears in Collections: | Journal/Magazine Article |
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