一种靶向乳腺癌干细胞线粒体功能并破坏其功能的铜（II）菲咯啉金属肽。
A Copper(II) Phenanthroline Metallopeptide That Targets and Disrupts Mitochondrial Function in Breast Cancer Stem Cells.
机构信息
Department of Chemistry, King's College London, London, SE1 1DB, UK.
Peptide Chemistry, The Francis Crick Institute, London, NW1 1AT, UK.
出版信息
Angew Chem Int Ed Engl. 2018 Jan 2;57(1):287-291. doi: 10.1002/anie.201710910. Epub 2017 Dec 5.
The breast cancer stem cell (CSC) and bulk breast cancer cell potency of a series of metallopeptides containing dichloro(1,10-phenanthroline)copper(II) and various organelle-targeting peptide sequences is reported. The mitochondria-targeting metallopeptide 1 exploits the higher mitochondrial load in breast CSCs over the corresponding non-CSCs and the vulnerability of breast CSCs to mitochondrial damage to potently and selectively kill breast CSCs. Strikingly, 1 reduces the formation and size of mammospheres to a greater extent than salinomycin, an established CSC-potent agent. Mechanistic studies show that 1 enters CSC mitochondria, induces mitochondrial dysfunction, generates reactive oxygen species (ROS), activates JNK and p38 pathways, and prompts apoptosis. To the best of our knowledge, 1 is the first metallopeptide to selectivity kill breast CSCs in vitro.
报道了一系列含二氯（1,10-菲咯啉）铜（II）和各种细胞器靶向肽序列的金属肽的乳腺癌干细胞（CSC）和批量乳腺癌细胞活力。线粒体靶向金属肽 1 利用乳腺癌 CSC 中线粒体负荷高于相应的非 CSC 以及乳腺癌 CSC 对线粒体损伤的脆弱性，有效地、选择性地杀死乳腺癌 CSC。引人注目的是，1 比盐霉素（一种已建立的 CSC 有效药物）更能减少类球体的形成和大小。机制研究表明，1 进入 CSC 线粒体，诱导线粒体功能障碍，产生活性氧（ROS），激活 JNK 和 p38 途径，并促使细胞凋亡。据我们所知，1 是第一个选择性地在体外杀死乳腺癌 CSC 的金属肽。
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