title: Cellular uptake, cytotoxicity, and metabolic profiling of human cancer cells treated with ruthenium(II) polypyridyl complexes [Ru(bpy)2(N--N)]Cl2 with N--N=bpy, phen, dpq, dppz, and dppn.
abstract: A series of five ruthenium(II) polypyridyl complexes [Ru(bpy)2(N--N)]Cl2 was tested against human HT-29 and MCF-7 cancer cell lines. Cellular uptake efficiency and cytotoxicity were found to increase with the size of the aromatic surface area of the N--N ligand. The most active compound carrying the dppn ligand exhibits a low micromolar IC(50) value against both cell lines comparable to that of cisplatin under similar conditions. Continuous measurement of oxygen consumption, extracellular acidification rate, and impedance of the cell layer with a chip-based sensor system upon exposure to the complexes showed only small changes for the first two parameters throughout the series. A significant and irreversible decrease in impedance was, however, found for the dppn compound. This suggests that its biological activity is related to modifications in cell morphology or cell-cell and cell-matrix contacts.
authors.affiliation: Lehrstuhl für Anorganische Chemie I-Bioanorganische Chemie, Ruhr-Universität Bochum NC 3/74, Universitätsstr. 150, 44801 Bochum, Germany. ulrich.schatzschneider@rub.de
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schatzschneider
authors.forename: Johanna
authors.initials: J
authors.lastname: Niesel
authors.forename: Ingo
authors.initials: I
authors.lastname: Ott
authors.forename: Ronald
authors.initials: R
authors.lastname: Gust
authors.forename: Hamed
authors.initials: H
authors.lastname: Alborzinia
authors.forename: Stefan
authors.initials: S
authors.lastname: Wölfl
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D011725:Pyridines; D012428:Ruthenium; C023666:pyridine; D002945:Cisplatin