Faculty of Chemistry, Jagiellonian University in Krakow, Gronostajowa 2, 30-387Krakow, Poland.
Department of Biophysical Microstructures, Institute of Nuclear Physics, Polish Academy of Sciences, PL-31342Krakow, Poland.
J Med Chem. 2022 Aug 11;65(15):10459-10470. doi: 10.1021/acs.jmedchem.2c00580. Epub 2022 Jul 27.
The effect of polypyridyl Ru(II) complexes on the ability of cancer cells to migrate and invade, two features important in the formation of metastases, is evaluated. studies are carried out on breast cancer cell lines, MDA-MB-231 and MCF-7, as well as melanoma cell lines A2058 and A375. Three Ru(II) complexes comprising two 4,7-diphenyl-1,10-phenanthroline (dip) ligands and as a third ligand 2,2'-bipyridine (bpy), or its derivative with either 4-[3-(2-nitro-1H-imidazol-1-yl)propyl] (bpy-NitroIm), or 5-(4-{4'-methyl-[2,2'-bipyridine]-4-yl}but-1-yn-1-yl)pyridine-2-carbaldehyde semicarbazone (bpy-SC) moiety attached are examined. The low sub-toxic doses of the studied compounds greatly affected the cancer cells by inhibiting cell detachment, migration, invasion, transmigration, and re-adhesion, as well as increasing cell elasticity. The molecular studies revealed that the Ru(II) polypyridyl complexes impact the activity of the selected integrins and upregulate the expression of focal adhesion components such as vinculin and paxillin, leading to an increased number of focal adhesion contacts.
研究了包含两个 4,7-二苯基-1,10-菲咯啉（dip）配体和一个 2,2'-联吡啶（bpy）或其具有 4-[3-(2-硝基-1H-咪唑-1-基)丙基]（bpy-NitroIm）或 5-(4-{4'-甲基-[2,2'-联吡啶]-4-基}丁-1-炔-1-基)吡啶-2-甲酰半缩氨（bpy-SC）部分的衍生物的三个 Ru(II) 配合物对癌细胞迁移和侵袭能力的影响，这两个特征在转移的形成中很重要。研究了乳腺癌细胞系 MDA-MB-231 和 MCF-7 以及黑色素瘤细胞系 A2058 和 A375。这些低亚毒性剂量的研究化合物通过抑制细胞脱落、迁移、侵袭、穿越和再黏附，以及增加细胞弹性，极大地影响了癌细胞。分子研究表明，Ru(II) 多吡啶配合物影响选定的整合素活性，并上调粘着斑成分（如 vinculin 和 paxillin）的表达，导致粘着斑接触点数量增加。
