title: The molecular mechanisms of antimetastatic ruthenium compounds explored through DIGE proteomics.
abstract: DIGE (difference in gel electrophoresis) proteomics is exploited here to gain insight into the molecular mechanisms of two established ruthenium-based antimetastatic agents, namely trans-[tetrachloro (DMSO) (imidazole)ruthenate(III)] (NAMI-A) and [Ru(η(6)-toluene)Cl(2)(PTA)] (RAPTA-T), where PTA is 1,3,5-triaza-7-phosphaadamantane. Following 24h exposure of A2780/S human ovarian carcinoma cells to pharmacologically relevant concentrations of either ruthenium compound, 2D-DIGE proteomic analysis evidenced only few differentially expressed proteins with respect to controls. Successive mass spectrometry measurements, MALDI-TOF (matrix assisted laser desorption ionization-time of flight) or LC-ESI/MS-MS (liquid chromatography-electrospray ionization/multi-stage mass spectrometry), allowed identification of most altered protein spots, some of which were associated to perturbations in specific cellular functions. Direct insight into the cellular effects of the investigated metallodrugs is thus achieved. Notably, the patterns of protein alterations induced by NAMI-A and RAPTA-T are quite similar to each other while being deeply different from those of cisplatin. To the best of our knowledge this is the first proteomic study on human cancer cells investigating responses to antimetastatic ruthenium drugs. The key role of new "omic" approaches for deciphering the elusive and complex biochemical mechanisms through which anticancer metallodrugs produce their pharmacological effects is further documented.
authors.affiliation: Department of Biochemical Sciences, University of Florence, viale G. Morgagni, 50, 50134 Firenze, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Guidi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Modesti
authors.forename: Ida
authors.initials: I
authors.lastname: Landini
authors.forename: Stefania
authors.initials: S
authors.lastname: Nobili
authors.forename: Enrico
authors.initials: E
authors.lastname: Mini
authors.forename: Luca
authors.initials: L
authors.lastname: Bini
authors.forename: Michele
authors.initials: M
authors.lastname: Puglia
authors.forename: Angela
authors.initials: A
authors.lastname: Casini
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dyson
authors.forename: Chiara
authors.initials: C
authors.lastname: Gabbiani
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D009362:Neoplasm Metastasis; D009942:Organometallic Compounds / Q000494:pharmacology*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D017975:Ruthenium Compounds; D053719:Tandem Mass Spectrometry; D057825:Two-Dimensional Difference Gel Electrophoresis; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D020543:Proteome; C534678:RAPTA-T; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D004121:Dimethyl Sulfoxide