文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

抗癌剂艾立布林对分离的哺乳动物线粒体的线粒体生物能量功能有直接影响。

The Anticancer Agent Elesclomol Has Direct Effects on Mitochondrial Bioenergetic Function in Isolated Mammalian Mitochondria.

机构信息

Department of Biology, Merrimack College, North Andover, MA 01845, USA.

Department of Health Sciences, Merrimack College, North Andover, MA 01845, USA.

出版信息

Biomolecules. 2019 Jul 24;9(8):298. doi: 10.3390/biom9080298.

DOI:10.3390/biom9080298
PMID:31344923
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6724019/
Abstract

Elesclomol ((-malonyl-bis(-methyl--thiobenzoylhydrazide)); formerly STA-4783) is a mitochondria-targeted chemotherapeutic agent that has demonstrated efficacy in selective cancer cell killing in pre-clinical and clinical testing. The biologically active form of elesclomol is a deprotonated copper chelate (elesclomol:copper; E:C), which has been shown to enhance reactive oxygen species (ROS) production and induce a transcriptional gene profile characteristic of an oxidative stress response in vitro. Previous studies suggest that E:C interacts with the electron transport chain (ETC) to generate high levels of ROS within the organelle and ultimately induce cell death. The purpose of this study was to further explore the mechanism of cellular and mitochondrial toxicity of E:C by examining its direct effect on mitochondrial bioenergetic function. The results obtained indicate that E:C treatment in whole cells of non-tumorigenic origin at high concentrations (40 M and higher) induces a rapid and substantial increase in mitochondrial superoxide levels and dissipation of mitochondrial membrane potential. Furthermore, similar higher concentrations of E:C act as a direct uncoupler of oxidative phosphorylation and generalized inhibitor of electron transport activity in isolated, intact mitochondria, and induce a dose-dependent inhibition of mitochondrial NADH-ubiquinone oxidoreductase activity in freeze-thawed mitochondrial preparations. The results of this study are important in that they are the first to demonstrate a direct effect of the E:C chelate on bioenergetic function in isolated mammalian mitochondria, and suggest the possibility that the increase in ROS production and cytotoxicity induced by E:C may in part be due to uncoupling of mitochondrial oxidative phosphorylation and/or inhibition of electron transport activity. These results also provide important information about the mechanisms of mitochondrial and cellular toxicity induced by E:C and will ultimately contribute to a better understanding of the therapeutic potential of elesclomol as an anticancer compound.

摘要

埃斯克罗莫尔（（-丙二酰基-双（-甲基--硫代苯甲酰基）肼）；以前称为 STA-4783）是一种靶向线粒体的化疗药物，已在临床前和临床试验中证明了其在选择性杀伤癌细胞方面的功效。埃斯克罗莫尔的生物活性形式是一种去质子化的铜配合物（埃斯克罗莫尔：铜；E:C），已被证明能增强活性氧（ROS）的产生，并诱导体外氧化应激反应的转录基因特征。先前的研究表明，E:C 与电子传递链（ETC）相互作用，在细胞器内产生高水平的 ROS，并最终诱导细胞死亡。本研究的目的是通过检查其对线粒体生物能功能的直接影响，进一步探讨 E:C 的细胞和线粒体毒性的机制。研究结果表明，在高浓度（40 μM 及以上）下，E:C 处理非致瘤源性细胞的整个细胞会迅速且大量增加线粒体中超氧化物的水平并耗散线粒体膜电位。此外，类似的较高浓度的 E:C 作为氧化磷酸化的直接解偶联剂和分离的完整线粒体中电子传递活性的通用抑制剂，诱导冻融线粒体制剂中线粒体 NADH-泛醌氧化还原酶活性的剂量依赖性抑制。本研究的结果很重要，因为它们首次证明了 E:C 配合物对分离的哺乳动物线粒体生物能功能的直接影响，并表明 E:C 诱导的 ROS 产生和细胞毒性增加可能部分归因于线粒体氧化磷酸化的解偶联和/或电子传递活性的抑制。这些结果还为 E:C 诱导的线粒体和细胞毒性的机制提供了重要信息，并将最终有助于更好地理解埃斯克罗莫尔作为抗癌化合物的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93cf/6724019/56a8bfc88985/biomolecules-09-00298-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93cf/6724019/ce91d8850791/biomolecules-09-00298-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93cf/6724019/01cf61f4123a/biomolecules-09-00298-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93cf/6724019/3ebb8408b5d1/biomolecules-09-00298-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93cf/6724019/bae8a324cfef/biomolecules-09-00298-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93cf/6724019/4a510d8a2e82/biomolecules-09-00298-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93cf/6724019/d271c5494f80/biomolecules-09-00298-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93cf/6724019/56a8bfc88985/biomolecules-09-00298-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93cf/6724019/ce91d8850791/biomolecules-09-00298-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93cf/6724019/01cf61f4123a/biomolecules-09-00298-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93cf/6724019/3ebb8408b5d1/biomolecules-09-00298-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93cf/6724019/bae8a324cfef/biomolecules-09-00298-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93cf/6724019/4a510d8a2e82/biomolecules-09-00298-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93cf/6724019/d271c5494f80/biomolecules-09-00298-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93cf/6724019/56a8bfc88985/biomolecules-09-00298-g007.jpg

相似文献

[1]
The Anticancer Agent Elesclomol Has Direct Effects on Mitochondrial Bioenergetic Function in Isolated Mammalian Mitochondria.

Biomolecules. 2019-7-24

[2]
The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells.

Free Radic Biol Med. 2012-4-17

[3]
Mitochondrial electron transport is the cellular target of the oncology drug elesclomol.

PLoS One. 2012-1-11

[4]
Pro-oxidant mitochondrial matrix-targeted ubiquinone MitoQ10 acts as anti-oxidant at retarded electron transport or proton pumping within Complex I.

Int J Biochem Cell Biol. 2009

[5]
High resolution respirometry analysis of polyethylenimine-mediated mitochondrial energy crisis and cellular stress: Mitochondrial proton leak and inhibition of the electron transport system.

Biochim Biophys Acta. 2013-10

[6]
Elesclomol induces cancer cell apoptosis through oxidative stress.

Mol Cancer Ther. 2008-8

[7]
Tumor cell death induced by the inhibition of mitochondrial electron transport: the effect of 3-hydroxybakuchiol.

Toxicol Appl Pharmacol. 2013-6-15

[8]
Elesclomol-induced increase of mitochondrial reactive oxygen species impairs glioblastoma stem-like cell survival and tumor growth.

J Exp Clin Cancer Res. 2021-7-12

[9]
Minerval (2-hydroxyoleic acid) causes cancer cell selective toxicity by uncoupling oxidative phosphorylation and compromising bioenergetic compensation capacity.

Biosci Rep. 2019-1-18

[10]
Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production.

Amino Acids. 2011-6-21

引用本文的文献

[1]
Cuproptosis-related genes and agents: implications in tumor drug resistance and future perspectives.

Front Pharmacol. 2025-5-8

[2]
Cuproplasia and cuproptosis in hepatocellular carcinoma: mechanisms, relationship and potential role in tumor microenvironment and treatment.

Cancer Cell Int. 2025-4-9

[3]
An up-To-Date Review of Elesclomol and Its Nano-Formulations in Cancer Therapy.

Cancer Rep (Hoboken). 2025-4

[4]
A novel prognostic scoring model based on cuproptosis identifies COMMD1 as a novel therapy target for liver hepatocellular carcinoma.

Oncol Res. 2025-2-28

[5]
The In Vitro Cytotoxic Effect of Elesclomol on Breast Adenocarcinoma Cells Is Enhanced by Concurrent Treatment with Glycolytic Inhibitors.

Cancers (Basel). 2024-12-3

[6]
Cuproptosis in cancer: biological implications and therapeutic opportunities.

Cell Mol Biol Lett. 2024-6-25

[7]
A Self-Amplifying ROS-Responsive Nanoplatform for Simultaneous Cuproptosis and Cancer Immunotherapy.

Adv Sci (Weinh). 2024-6

[8]
Perturbation of Copper Homeostasis Sensitizes Cancer Cells to Elevated Temperature.

Int J Mol Sci. 2023-12-28

[9]
A cautionary note on the use of N-acetylcysteine as a reactive oxygen species antagonist to assess copper mediated cell death.

PLoS One. 2023

[10]
Elesclomol, a copper-transporting therapeutic agent targeting mitochondria: from discovery to its novel applications.

J Transl Med. 2023-10-20

本文引用的文献

[1]
Mitochondrial metabolism promotes adaptation to proteotoxic stress.

Nat Chem Biol. 2019-5-27

[2]
The evaluation of the anti-cancer drug elesclomol that forms a redox-active copper chelate as a potential anti-tubercular drug.

IUBMB Life. 2019-1-14

[3]
Elesclomol restores mitochondrial function in genetic models of copper deficiency.

Proc Natl Acad Sci U S A. 2018-7-23

[4]
The Mitochondrial Complex(I)ty of Cancer.

Front Oncol. 2017-6-8

[5]
A phase I study of elesclomol sodium in patients with acute myeloid leukemia.

Leuk Lymphoma. 2016-10

[6]
Treatment Strategies that Enhance the Efficacy and Selectivity of Mitochondria-Targeted Anticancer Agents.

Int J Mol Sci. 2015-7-29

[7]
The mitochondrial permeability transition pore: molecular nature and role as a target in cardioprotection.

J Mol Cell Cardiol. 2015-1

[8]
Syntheses and antitumor activities of N'1,N'3-dialkyl-N'1,N'3-di-(alkylcarbonothioyl) malonohydrazide: the discovery of elesclomol.

Bioorg Med Chem Lett. 2013-7-25

[9]
Final results of phase III SYMMETRY study: randomized, double-blind trial of elesclomol plus paclitaxel versus paclitaxel alone as treatment for chemotherapy-naive patients with advanced melanoma.

J Clin Oncol. 2013-2-11

[10]
Assessment of mitochondrial respiratory chain enzymatic activities on tissues and cultured cells.

Nat Protoc. 2012-5-31

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索