title: Preclinical activity of multiple-target gold(III)-dithiocarbamato peptidomimetics in prostate cancer cells and xenografts.
abstract: BACKGROUND
  Recently, novel gold(III)-dithiocarbamato peptidomimetics, designed to target peptide transporters upregulated in several tumor cells have shown promise as anticancer agents.
  
  
  RESULTS
  The biological behavior of the most promising derivatives AuD8 and AuD9 was studied in PC3 and DU145 prostate cancer cells. They exert higher cytotoxicity in vitro than the reference drug cisplatin and induce apoptosis, promoting mitochondrial membrane permeabilization and stimulating reactive oxygen species generation. Moreover, they inhibit both selenoenzyme thioredoxin reductase and proteasome activity. Additionally, AuD8 effectively reduces tumor growth in prostate tumor-bearing nude mice with minimal systemic toxicity.
  
  
  CONCLUSIONS
  Altogether, our results provide insights into the anticancer activity of these gold(III)-dithiocarbamato peptidomimetics and support their potential as new agents for prostate cancer treatment.
authors.affiliation: Centro di Riferimento Oncologico, IRCCS, National Cancer Institute, Experimental Oncology 2, Via F. Gallini 2, Aviano (PN), 33081, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Celegato
authors.forename: Dolores
authors.initials: D
authors.lastname: Fregona
authors.forename: Maurizio
authors.initials: M
authors.lastname: Mongiat
authors.forename: Luca
authors.initials: L
authors.lastname: Ronconi
authors.forename: Cinzia
authors.initials: C
authors.lastname: Borghese
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Canzonieri
authors.forename: Naike
authors.initials: N
authors.lastname: Casagrande
authors.forename: Chiara
authors.initials: C
authors.lastname: Nardon
authors.forename: Alfonso
authors.initials: A
authors.lastname: Colombatti
authors.forename: Donatella
authors.initials: D
authors.lastname: Aldinucci
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017612:Gold Compounds / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D009368:Neoplasm Transplantation; D057786:Peptidomimetics / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D017382:Reactive Oxygen Species; D013859:Thiocarbamates / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D017612:Gold Compounds; D057786:Peptidomimetics; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; D020169:Caspases