线粒体靶向抗生素对癌细胞线粒体功能和增殖的影响
Impact of Mitochondrial Targeting Antibiotics on Mitochondrial Function and Proliferation of Cancer Cells.
作者信息
Cochrane Edward J, Hulit James, Lagasse Franz P, Lechertier Tanguy, Stevenson Brett, Tudor Corina, Trebicka Diana, Sparey Tim, Ratcliffe Andrew J
机构信息
Department of Chemistry, Sygnature Discovery, BioCity, Pennyfoot Street, Nottingham NG1 1GR, United Kingdom.
Novintum Biosciences Ltd, London Bioscience Innovation Centre, 2 Royal College Street, London, NW1 0NH, United Kingdom.
出版信息
ACS Med Chem Lett. 2021 Mar 8;12(4):579-584. doi: 10.1021/acsmedchemlett.0c00632. eCollection 2021 Apr 8.
Abstract
Some marketed antibiotics can cause mitochondria dysfunction via inhibition of the mitochondrial translation process. There is great interest in exploiting such effects within a cancer setting. To enhance accumulation of antibiotics within the mitochondria of cancer cells, and therefore delivery of a greater potency payload, a mitochondrial targeting group in the form of a triphenylphosphonium (TPP) cation was appended via an alkyl chain length consisting of 7 to 11 carbons to the ribosomal antibiotics azithromycin and doxycycline. Using MDA-MB-231 cells, the effects of each subseries on mitochondrial translation, mitochondrial bioenergetics, and cell viability are described.
摘要
一些已上市的抗生素可通过抑制线粒体翻译过程导致线粒体功能障碍。人们对在癌症环境中利用这种效应非常感兴趣。为了增强抗生素在癌细胞线粒体内的积累，从而传递更大效力的有效载荷，通过由7至11个碳原子组成的烷基链，将三苯基鏻（TPP）阳离子形式的线粒体靶向基团连接到核糖体抗生素阿奇霉素和强力霉素上。利用MDA-MB-231细胞，描述了每个子系列对线粒体翻译、线粒体生物能量学和细胞活力的影响。
相似文献
1
Impact of Mitochondrial Targeting Antibiotics on Mitochondrial Function and Proliferation of Cancer Cells.线粒体靶向抗生素对癌细胞线粒体功能和增殖的影响
ACS Med Chem Lett. 2021 Mar 8;12(4):579-584. doi: 10.1021/acsmedchemlett.0c00632. eCollection 2021 Apr 8.
2
Complex Mitochondrial Dysfunction Induced by TPP-Gentisic Acid and Mitochondrial Translation Inhibition by Doxycycline Evokes Synergistic Lethality in Breast Cancer Cells.TPP-龙胆酸诱导的复杂线粒体功能障碍和强力霉素抑制线粒体翻译在乳腺癌细胞中引发协同致死作用。
Cells. 2020 Feb 11;9(2):407. doi: 10.3390/cells9020407.
3
The Anti-Cancer Effects of Mitochondrial-Targeted Triphenylphosphonium-Resveratrol Conjugate on Breast Cancer Cells.线粒体靶向三苯基鏻-白藜芦醇共轭物对乳腺癌细胞的抗癌作用
Pharmaceuticals (Basel). 2022 Oct 15;15(10):1271. doi: 10.3390/ph15101271.
4
Assessing mitochondria-targeted acyl hydroquinones on the mitochondrial platelet function and cytotoxic activity: Role of the linker length.评估线粒体靶向酰基对苯二酚对线粒体血小板功能和细胞毒性活性的影响：连接子长度的作用。
Free Radic Biol Med. 2023 Nov 1;208:26-36. doi: 10.1016/j.freeradbiomed.2023.07.030. Epub 2023 Jul 27.
5
Doxycycline, Azithromycin and Vitamin C (DAV): A potent combination therapy for targeting mitochondria and eradicating cancer stem cells (CSCs).强力霉素、阿奇霉素和维生素C（DAV）：一种靶向线粒体并根除癌症干细胞（CSC）的有效联合疗法。
Aging (Albany NY). 2019 Apr 19;11(8):2202-2216. doi: 10.18632/aging.101905.
6
Effect of the Conjugation Density of Triphenylphosphonium Cation on the Mitochondrial Targeting of Poly(amidoamine) Dendrimers.三苯基鏻阳离子共轭密度对聚（酰胺胺）树枝状大分子线粒体靶向性的影响。
Mol Pharm. 2015 Aug 3;12(8):3043-53. doi: 10.1021/acs.molpharmaceut.5b00320. Epub 2015 Jul 21.
7
Mitochondrial delivery of doxorubicin via triphenylphosphine modification for overcoming drug resistance in MDA-MB-435/DOX cells.通过三苯基膦修饰实现阿霉素的线粒体递送以克服MDA-MB-435/DOX细胞中的耐药性。
Mol Pharm. 2014 Aug 4;11(8):2640-9. doi: 10.1021/mp500038g. Epub 2014 May 19.
8
Conjugation of Triphenylphosphonium Cation to Hydrophobic Moieties to Prepare Mitochondria-Targeting Nanocarriers.将三苯基鏻阳离子与疏水部分共轭以制备线粒体靶向纳米载体。
Methods Mol Biol. 2019;2000:183-189. doi: 10.1007/978-1-4939-9516-5_12.
9
Mitochondrial Delivery of Phenol Substructure Triggers Mitochondrial Depolarization and Apoptosis of Cancer Cells.
Front Pharmacol. 2018 Jun 4;9:580. doi: 10.3389/fphar.2018.00580. eCollection 2018.
10
Mitochondrial Targeted Doxorubicin-Triphenylphosphonium Delivered by Hyaluronic Acid Modified and pH Responsive Nanocarriers to Breast Tumor: in Vitro and in Vivo Studies.基于透明质酸修饰的 pH 响应纳米载体的线粒体靶向多柔比星-三苯基膦递药系统用于治疗乳腺癌的体外与体内研究。
Mol Pharm. 2018 Mar 5;15(3):882-891. doi: 10.1021/acs.molpharmaceut.7b00793. Epub 2018 Feb 1.
引用本文的文献
1
The Role of HSP90 and TRAP1 Targets on Treatment in Hepatocellular Carcinoma.热休克蛋白90（HSP90）和肿瘤坏死因子受体相关蛋白1（TRAP1）靶点在肝细胞癌治疗中的作用
Mol Biotechnol. 2025 Apr;67(4):1367-1381. doi: 10.1007/s12033-024-01151-4. Epub 2024 Apr 29.
2
Triphenylphosphonium Analogs of Short Peptide Related to Bactenecin 7 and Oncocin 112 as Antimicrobial Agents.与杆菌防御素7和癌抑素112相关的短肽的三苯基鏻类似物作为抗菌剂
Pharmaceutics. 2024 Jan 22;16(1):148. doi: 10.3390/pharmaceutics16010148.
3
Azithromycin inhibits glioblastoma angiogenesis in mice via inducing mitochondrial dysfunction and oxidative stress.阿奇霉素通过诱导线粒体功能障碍和氧化应激抑制小鼠脑胶质母细胞瘤血管生成。
Cancer Chemother Pharmacol. 2023 Oct;92(4):291-302. doi: 10.1007/s00280-023-04567-y. Epub 2023 Jul 24.
4
Glycogen synthase 1 targeting reveals a metabolic vulnerability in triple-negative breast cancer.靶向糖原合酶 1 揭示了三阴性乳腺癌的代谢脆弱性。
J Exp Clin Cancer Res. 2023 Jun 6;42(1):143. doi: 10.1186/s13046-023-02715-z.
5
Hypoxia Regulates Endogenous Double-Stranded RNA Production Reduced Mitochondrial DNA Transcription.缺氧调节内源性双链RNA生成并减少线粒体DNA转录。
Front Oncol. 2021 Nov 24;11:779739. doi: 10.3389/fonc.2021.779739. eCollection 2021.
6
Rational Design 2-Hydroxypropylphosphonium Salts as Cancer Cell Mitochondria-Targeted Vectors: Synthesis, Structure, and Biological Properties.理性设计 2-羟丙基膦盐作为癌细胞线粒体靶向载体：合成、结构和生物学性质。
Molecules. 2021 Oct 20;26(21):6350. doi: 10.3390/molecules26216350.
本文引用的文献
1
A Novel Triphenylphosphonium Carrier to Target Mitochondria without Uncoupling Oxidative Phosphorylation.一种新型三苯基膦载体，可靶向线粒体而不解偶联氧化磷酸化。
J Med Chem. 2021 Jan 14;64(1):662-676. doi: 10.1021/acs.jmedchem.0c01671. Epub 2021 Jan 4.
2
Inhibition of mitochondrial respiration by tigecycline selectively targets thyroid carcinoma and increases chemosensitivity.替加环素通过抑制线粒体呼吸，选择性地靶向甲状腺癌并增加化疗敏感性。
Clin Exp Pharmacol Physiol. 2019 Oct;46(10):890-897. doi: 10.1111/1440-1681.13126. Epub 2019 Jul 31.
3
Inhibition of mitochondrial translation as a therapeutic strategy for human ovarian cancer to overcome chemoresistance.抑制线粒体翻译作为克服人卵巢癌化疗耐药性的治疗策略。
Biochem Biophys Res Commun. 2019 Feb 5;509(2):373-378. doi: 10.1016/j.bbrc.2018.12.127. Epub 2018 Dec 25.
4
A review of the basics of mitochondrial bioenergetics, metabolism, and related signaling pathways in cancer cells: Therapeutic targeting of tumor mitochondria with lipophilic cationic compounds.癌症细胞中线粒体生物能量学、代谢和相关信号通路的基础研究综述：亲脂阳离子化合物对肿瘤线粒体的治疗靶向作用。
Redox Biol. 2018 Apr;14:316-327. doi: 10.1016/j.redox.2017.09.020. Epub 2017 Sep 29.
5
Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemia stem cells.靶向线粒体氧化磷酸化可根除耐治疗的慢性髓性白血病干细胞。
Nat Med. 2017 Oct;23(10):1234-1240. doi: 10.1038/nm.4399. Epub 2017 Sep 18.
6
Mitochondrial dysfunction and potential anticancer therapy.线粒体功能障碍与潜在的抗癌治疗。
Med Res Rev. 2017 Nov;37(6):1275-1298. doi: 10.1002/med.21459. Epub 2017 Jul 6.
7
Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications.线粒体靶向的三苯基鏻基化合物：合成、作用机制及治疗与诊断应用
Chem Rev. 2017 Aug 9;117(15):10043-10120. doi: 10.1021/acs.chemrev.7b00042. Epub 2017 Jun 27.
8
Inhibition of mitochondrial translation effectively sensitizes renal cell carcinoma to chemotherapy.抑制线粒体翻译可有效使肾细胞癌对化疗敏感。
Biochem Biophys Res Commun. 2017 Aug 26;490(3):767-773. doi: 10.1016/j.bbrc.2017.06.115. Epub 2017 Jun 20.
9
Antibiotic tigecycline enhances cisplatin activity against human hepatocellular carcinoma through inducing mitochondrial dysfunction and oxidative damage.抗生素替加环素通过诱导线粒体功能障碍和氧化损伤增强顺铂对人肝癌的活性。
Biochem Biophys Res Commun. 2017 Jan 29;483(1):17-23. doi: 10.1016/j.bbrc.2017.01.021. Epub 2017 Jan 6.
10
Mitochondria-Targeted Analogues of Metformin Exhibit Enhanced Antiproliferative and Radiosensitizing Effects in Pancreatic Cancer Cells.二甲双胍的线粒体靶向类似物在胰腺癌细胞中表现出增强的抗增殖和放射增敏作用。
Cancer Res. 2016 Jul 1;76(13):3904-15. doi: 10.1158/0008-5472.CAN-15-2534. Epub 2016 May 23.
Zotero 插件