Elumalai Palani, Kaushik Neha, Kim Dong Hwan, Kim Hyunuk, Lee Su Jae, Choi Eun Ha, Chi Ki-Whan, Kaushik Nagendra Kumar
Department of Chemistry, University of Ulsan, Ulsan, Republic of Korea.
Department of Chemistry, Texas A&M University at Qatar, Doha, Qatar.
Oncotarget. 2017 Jul 5;8(36):60188-60200. doi: 10.18632/oncotarget.19028. eCollection 2017 Sep 1.
The tumorigenic potentials of residual cancer stem-like cells within tumors represent limitations of current cancer therapies. Here, the authors describe the effects of synthesized flexible, ligated, supramolecular self-assembled chair type tetranuclear ruthenium (II) metallacycles (2-5) on glioblastoma and glioma stem like cells. These self-assemblies were observed to be selectively toxic to glioma cells and CD133-positive glioma stem like cells population. Of the self-assembled compounds tested, metallacycle 4 more efficiently induced glioma stem like cells death within a brain cancer cell population and simultaneously inhibited the formation of free-floating gliospheres by reducing the sphere size. Detailed cell death studies revealed that treatment with metallacycle 4 reduced mitochondrial membrane potentials (an indicator of apoptosis) of glioma stem like cells. These results shows the elimination of cancer stem-like cells using an appropriate ligand binding adaptor offers a potential means of developing metal-based compounds for the treatment of chemo-resistant tumors.
肿瘤内残留的癌症干细胞样细胞的致瘤潜力是当前癌症治疗的局限性所在。在此,作者描述了合成的柔性、连接的、超分子自组装椅型四核钌(II)金属环化物(2-5)对胶质母细胞瘤和胶质瘤干细胞样细胞的影响。观察到这些自组装体对胶质瘤细胞和CD133阳性胶质瘤干细胞样细胞群体具有选择性毒性。在所测试的自组装化合物中,金属环化物4在脑癌细胞群体中更有效地诱导胶质瘤干细胞样细胞死亡,同时通过减小球体大小抑制游离胶质瘤球的形成。详细的细胞死亡研究表明,用金属环化物4处理可降低胶质瘤干细胞样细胞的线粒体膜电位(细胞凋亡的一个指标)。这些结果表明,使用合适的配体结合适配器消除癌症干细胞样细胞为开发用于治疗化疗耐药肿瘤的金属基化合物提供了一种潜在方法。