Selectively attacking tumor cells of Ru/Ir–arene complexes based on meclofenamic acid via cyclooxygenase-2 inhibition,Dalton Transactions

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Selectively attacking tumor cells of Ru/Ir–arene complexes based on meclofenamic acid via cyclooxygenase-2 inhibition
Dalton Transactions ( IF 3.5 ) Pub Date : 2023-04-21 , DOI: 10.1039/d3dt00282a
Yuanlei Huang ₁ , Mengdi Lv ₁ , Binglian Guo ₁ , Guojing Hu ₁ , Yong Qian ₁ , Zhi Su ₁ , Xuling Xue ₁ , Hong-Ke Liu ₁

Affiliation

Breast cancer (BC) is one of the most common malignant tumors and often accompanied by inflammatory processes. Inflammation is an essential component of the tumor microenvironment, which might influence tumor proliferation and metastasis. Herein, three metal–arene complexes MA-bip-Ru, MA-bpy-Ir, and MA-bpy-Ru were prepared by tethering the non-steroidal anti-inflammatory drug meclofenamic acid (MA). Among them, MA-bip-Ru and MA-bpy-Ir showed lower cytotoxicity towards cancer cells, but MA-bpy-Ru showed significantly high selectivity and cytotoxicity towards MCF-7 cells through the autophagic pathway and exhibited no toxicity against normal HLF cells, showing potential for selective treatment of tumor cells. MA-bpy-Ru could also effectively destroy the 3D multicellular tumor spheroids, demonstrating its potential for clinical application. Besides, MA-bip-Ru, MA-bpy-Ir, and MA-bpy-Ru exhibited anti-inflammatory properties superior to MA, notably downregulating the expression of cyclooxygenase-2 (COX-2) and inhibiting the secretion of prostaglandin E2 in vitro. These findings demonstrated that MA-bpy-Ru was capable of intervening in inflammatory processes and showed the potential of MA-bpy-Ru to act as a selective anticancer agent, thus presenting a new mechanism of action for metal–arene complexes.

中文翻译：

基于甲氯芬那酸的 Ru/Ir-芳烃配合物通过环氧合酶 2 抑制选择性攻击肿瘤细胞

乳腺癌 (BC) 是最常见的恶性肿瘤之一，通常伴有炎症过程。炎症是肿瘤微环境的重要组成部分，可能影响肿瘤的增殖和转移。在此，通过束缚非甾体抗炎药甲氯芬那酸 (MA) 制备了三种金属芳烃配合物MA-bip-Ru、MA-bpy-Ir和MA-bpy-Ru 。其中，MA-bip-Ru和MA-bpy-Ir对癌细胞表现出较低的细胞毒性，但MA-bpy-Ru通过自噬途径对 MCF-7 细胞显示出显着的高选择性和细胞毒性，并且对正常 HLF 细胞无毒性，显示出选择性治疗肿瘤细胞的潜力。MA-bpy-Ru还可以有效地破坏 3D 多细胞肿瘤球体，展示了其临床应用潜力。此外，MA-bip-Ru、MA-bpy-Ir和MA-bpy-Ru表现出优于 MA 的抗炎特性，尤其是下调环氧合酶 2 (COX-2) 的表达并抑制前列腺素 E2 的分泌。体外。这些发现表明MA-bpy-Ru能够干预炎症过程，并显示出MA-bpy-Ru作为选择性抗癌剂的潜力，从而为金属-芳烃配合物提供了一种新的作用机制。

更新日期：2023-04-21

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