Anticancer copper complex with nucleus, mitochondrion and cyclooxygenase-2 as multiple targets.,Journal of Inorganic Biochemistry

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Anticancer copper complex with nucleus, mitochondrion and cyclooxygenase-2 as multiple targets.
Journal of Inorganic Biochemistry ( IF 3.8 ) Pub Date : 2018-10-15 , DOI: 10.1016/j.jinorgbio.2018.10.003
Xiangchao Shi ₁ , Hongbao Fang ₁ , Yan Guo ₁ , Hao Yuan ₁ , Zijian Guo ₁ , Xiaoyong Wang ₂

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Copper complexes are hopeful anticancer drugs due to their multifacet biological properties and high biocompatibility. Inflammatory environment plays an important role in tumor progression and affects the body response to chemotherapeutic agents. A copper(II) complex CuLA with a phenanthroline derivative N-(1,10-phenanthrolin-5-yl)-nonanamide (L) and two aspirin anions (A) as the ligands was synthesized. CuLA effectively induces mitochondrial dysfunction and promotes early-apoptosis in SKOV-3 cells; moreover, it suppresses the expression of cyclooxygenase-2, a key enzyme involved in inflammatory response, in lipopolysaccharide stimulated RAW 264.7 cells. By contrast, the analogue complex CuL without aspirin ligand shows similar influences on cellular redox homeostasis and cell cycle progression but relatively low cytotoxic activity due to its mild effect on mitochondrial function; more importantly, it lacks inhibition to cyclooxygenase-2. The results demonstrate that CuLA inhibits cancer cells through dual pathways involving DNA damage and mitochondrial dysfunction. The introduction of aspirin not only enhances the antitumour efficacy but also reduces the inflammatory threat. Copper complexes with both antitumor and anti-inflammatory activities may represent a new type of multifunctional metal complexes in hope to be developed into novel metallodrugs.

中文翻译：

以核，线粒体和环氧合酶2为多个靶点的抗癌铜络合物。

铜配合物由于具有多方面的生物学特性和高度的生物相容性，因此是有希望的抗癌药物。炎性环境在肿瘤进展中起重要作用，并影响机体对化学治疗剂的反应。合成了具有菲咯啉衍生物N-（1,10-菲咯啉-5-基）-壬酰胺（L）和两个阿司匹林阴离子（A）作为配体的铜（II）配合物CuLA。CuLA有效诱导线粒体功能障碍并促进SKOV-3细胞的早期凋亡。此外，它抑制脂多糖刺激的RAW 264.7细胞中与炎症反应有关的关键酶环氧合酶2的表达。相比之下，没有阿司匹林配体的类似物复合物CuL对细胞氧化还原稳态和细胞周期进程具有相似的影响，但由于其对线粒体功能的温和作用，其细胞毒性活性相对较低；更重要的是，它缺乏对环氧合酶2的抑制作用。结果表明，CuLA通过涉及DNA损伤和线粒体功能障碍的双重途径抑制癌细胞。阿司匹林的引入不仅增强了抗肿瘤功效，还减少了炎症威胁。具有抗肿瘤和抗炎活性的铜配合物可能代表了一种新型的多功能金属配合物，希望被开发成新型的金属药物。结果表明，CuLA通过涉及DNA损伤和线粒体功能障碍的双重途径抑制癌细胞。阿司匹林的引入不仅增强了抗肿瘤功效，还减少了炎症威胁。具有抗肿瘤和抗炎活性的铜配合物可能代表了一种新型的多功能金属配合物，希望被开发成新型的金属药物。结果表明，CuLA通过涉及DNA损伤和线粒体功能障碍的双重途径抑制癌细胞。阿司匹林的引入不仅增强了抗肿瘤功效，还减少了炎症威胁。具有抗肿瘤和抗炎活性的铜配合物可能代表了一种新型的多功能金属配合物，希望被开发成新型的金属药物。

更新日期：2018-10-15

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