title: Clioquinol-ruthenium complex impairs tumour cell invasion by inhibiting cathepsin B activity.
abstract: Over the past few years, the organometalled compounds, including ruthenium, gained a lot of attention as anticancer agents. We report on the clioquinol-ruthenium complex [Ru(η6-p-cymene)(Cq)Cl] as a potent inhibitor of cathepsin B, a lysosomal cysteine peptidase, involved in tumour cell invasion and metastasis. In the low micromolar concentration range, the clioquinol-ruthenium complex did not exhibit cytotoxic effects on MCF-10A neoT and U-87 MG cells; it did, however, significantly reduce their ability for extracellular matrix degradation and invasiveness in two independent cell-based models, measuring either electrical impedance in real time or the growth of multicellular tumour spheroids implanted in Matrigel, a model representing the extracellular matrix. These results establish ruthenium based organometallic compounds as promising candidates for further pre-clinical studies as anticancer therapeutics.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia. janko.kos@ffa.uni-lj.si.
authors.forename: Ana
authors.initials: A
authors.lastname: Mitrović
authors.forename: Jakob
authors.initials: J
authors.lastname: Kljun
authors.forename: Izidor
authors.initials: I
authors.lastname: Sosič
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gobec
authors.forename: Iztok
authors.initials: I
authors.lastname: Turel
authors.forename: Janko
authors.initials: J
authors.lastname: Kos
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002401:Cathepsin B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D007464:Clioquinol / Q000031:analogs & derivatives / Q000494:pharmacology*; D000081007:Cymenes; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000081007:Cymenes; D004791:Enzyme Inhibitors; D039821:Monoterpenes; D009942:Organometallic Compounds; C007210:4-cymene; D007464:Clioquinol; D012428:Ruthenium; D002401:Cathepsin B