title: Effect of cisplatin on proteasome activity.
abstract: Cisplatin is a widely used chemotherapy drug which exerts cytotoxic activity by affecting both nuclear and cytosolic pathways. Herewith, we report, for the first time, that cisplatin inhibits proteasome activity in vitro. Cisplatin induces a dose dependent inhibition of the three enzymatic activities of proteasome (i.e., the chymotrypsin-like activity, the trypsin-like activity and the caspase-like activity). Moreover, cisplatin administration to neuroblastoma cells brings about a fast loss of proteasome particle activity, which is followed by a de novo synthesis of proteasome. Lastly, we report that the simultaneous administration of lactacystin and cisplatin enhances the cytotoxicity of cisplatin alone. The overall bulk of data opens to an intriguing scenario, concerning the biological effects of cisplatin in the control of cellular life, which goes beyond the well established genotoxic effect.
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy; CIRCMSB, Via C. Ulpiani 27, I-70125 Bari, Italy.
authors.forename: G R
authors.initials: GR
authors.lastname: Tundo
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy; CIRCMSB, Via C. Ulpiani 27, I-70125 Bari, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Sbardella
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy; CIRCMSB, Via C. Ulpiani 27, I-70125 Bari, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ciaccio
authors.affiliation: CIRCMSB, Via C. Ulpiani 27, I-70125 Bari, Italy; Department of Environmental Biological Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Italy.
authors.forename: S
authors.initials: S
authors.lastname: De Pascali
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Campanella
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Cozza
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy; Center for Space Biomedicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy.
authors.forename: U
authors.initials: U
authors.lastname: Tarantino
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy; CIRCMSB, Via C. Ulpiani 27, I-70125 Bari, Italy; Center for Space Biomedicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Coletta
authors.affiliation: CIRCMSB, Via C. Ulpiani 27, I-70125 Bari, Italy; Department of Environmental Biological Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Italy.
authors.forename: F P
authors.initials: FP
authors.lastname: Fanizzi
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy; CIRCMSB, Via C. Ulpiani 27, I-70125 Bari, Italy; Center for Space Biomedicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy. Electronic address: Stefano.marini@uniroma2.it.
authors.forename: S
authors.initials: S
authors.lastname: Marini
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D054875:Ubiquitination
chemical_list: D000970:Antineoplastic Agents; D015853:Cysteine Proteinase Inhibitors; D061988:Proteasome Inhibitors; C067713:lactacystin; D046988:Proteasome Endopeptidase Complex; D002945:Cisplatin; D000111:Acetylcysteine
keywords: Cisplatin; Lactacystin; Neuroblastoma,; Proteasome