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SIRT1介导的线粒体和Akt通路在黄栌黄酮纳米脂质体诱导的胶质母细胞瘤细胞死亡中的作用

Role of SIRT1-mediated mitochondrial and Akt pathways in glioblastoma cell death induced by Cotinus coggygria flavonoid nanoliposomes.

作者信息

Wang Gang, Wang Jun Jie, To Tony S S, Zhao Hua Fu, Wang Jing

机构信息

Department of Pharmaceutics, Shanghai Eighth People's Hospital, Shanghai, People's Republic of China ; College of Pharmacy, Hubei University of Medicine, Shiyan, Hubei Province, People's Republic of China.

Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, People's Republic of China.

出版信息

Int J Nanomedicine. 2015 Aug 4;10:5005-23. doi: 10.2147/IJN.S82282. eCollection 2015.

DOI:10.2147/IJN.S82282
PMID:26345416
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4531020/
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.

摘要

黄酮类化合物是黄栌（CC）中的主要多酚成分，在我们之前的研究中已发现其具有抗癌作用；然而，诱导人胶质母细胞瘤（GBM）细胞死亡的确切机制仍有待解决。在本研究中，开发了一种新型的负载黄栌黄酮（CCFs）的聚乙烯吡咯烷酮K - 30/十二烷基硫酸钠和聚乙二醇包被脂质体，以提高其溶解度和抗脑肿瘤效果，并研究了CCF纳米脂质体（CCF - NLs）在体外诱导凋亡细胞死亡的分子机制。用CCF - NLs处理的DBTRG - 05MG GBM细胞系显示出潜在的抗增殖作用。关于在DBTRG - 05MG GBM细胞中诱导凋亡的潜在机制，CCF - NLs被证明可下调抗凋亡B细胞淋巴瘤/白血病2（Bcl - 2）的表达，Bcl - 2是一种凋亡相关蛋白家族成员，但与对照组相比，促凋亡的Bcl - 2相关X蛋白的表达增强。CCF - NLs还抑制了半胱天冬酶 - 3和 - 9的活性，它们分别是外在和内在凋亡途径的起始半胱天冬酶。半胱天冬酶激活的阻断持续诱导CCF - NL处理的DBTRG - 05MG细胞凋亡并抑制其生长。本研究进一步研究了Akt通路在CCF - NLs诱导的凋亡细胞死亡中的作用，结果表明CCF - NLs使Akt失活。具体而言，CCF - NLs下调了p - Akt和SIRT1的表达以及磷酸化p53的水平。总之，这些结果表明在DBTRG - 05MG细胞中，CCF - NLs诱导了SIRT1/p53介导的细胞死亡，而非细胞外信号调节激酶介导的细胞死亡。总体而言，本研究表明，CCF - NLs可能通过阻断SIRT1/p53介导的线粒体和Akt通路，依赖半胱天冬酶激活内在和外在信号通路，从而在DBTRG - 05MG GBM细胞中发挥促凋亡作用。

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本文引用的文献

1
Chemoprevention of prostate cancer by major dietary phytochemicals.植物化学物通过主要饮食预防前列腺癌。
Anticancer Res. 2013 Oct;33(10):4163-74.
2
Dietary epigenetics in cancer and aging.癌症与衰老中的饮食表观遗传学
Cancer Treat Res. 2014;159:257-67. doi: 10.1007/978-3-642-38007-5_15.
3
The JAK2/STAT3 and mitochondrial pathways are essential for quercetin nanoliposome-induced C6 glioma cell death.槲皮素纳米脂质体诱导 C6 神经胶质瘤细胞死亡与 JAK2/STAT3 和线粒体途径有关。
近期关于突变型 p53 的研究进展：揭示新的致癌作用、降解途径和治疗干预措施。
Biomolecules. 2024 May 31;14(6):649. doi: 10.3390/biom14060649.
4
Mitoepigenetics and gliomas: epigenetic alterations to mitochondrial DNA and nuclear DNA alter mtDNA expression and contribute to glioma pathogenicity.线粒体表观遗传学与神经胶质瘤：线粒体DNA和核DNA的表观遗传改变会改变线粒体DNA的表达，并促进神经胶质瘤的致病性。
Front Neurol. 2023 May 30;14:1154753. doi: 10.3389/fneur.2023.1154753. eCollection 2023.
5
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CNS Neurosci Ther. 2023 Sep;29(9):2583-2596. doi: 10.1111/cns.14198. Epub 2023 Apr 5.
6
Sirtuins and Hypoxia in EMT Control.Sirtuins与上皮-间质转化调控中的缺氧
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10
Emodin protects H9c2 cells from hypoxia-induced injury by up-regulating miR-138 expression.大黄素通过上调miR-138表达保护H9c2细胞免受缺氧诱导的损伤。
Braz J Med Biol Res. 2019 Feb 25;52(3):e7994. doi: 10.1590/1414-431X20187994.
Cell Death Dis. 2013 Aug 1;4(8):e746. doi: 10.1038/cddis.2013.242.
4
Methanol extract from the stem of Cotinus coggygria Scop., and its major bioactive phytochemical constituent myricetin modulate pyrogallol-induced DNA damage and liver injury.从黄栌茎中提取的甲醇提取物及其主要生物活性植物化学成分杨梅素可调节连苯三酚诱导的 DNA 损伤和肝损伤。
Mutat Res. 2013 Aug 15;755(2):81-9. doi: 10.1016/j.mrgentox.2013.03.011. Epub 2013 Jul 2.
5
Liposomal encapsulation of the natural flavonoid fisetin improves bioavailability and antitumor efficacy.脂质体包封天然类黄酮非瑟酮可提高生物利用度和抗肿瘤疗效。
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6
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7
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9
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