title: Antitumour and antiangiogenic activities of [Pt(O,O'-acac)(γ-acac)(DMS)] in a xenograft model of human renal cell carcinoma.
abstract: It is thought that the mechanism of action of anticancer chemotherapeutic agents is mainly due to a direct inhibition of tumour cell proliferation. In tumour specimens, the endothelial cell proliferation rate increases, suggesting that the therapeutic effects of anticancer agents could also be attributed to inhibition of tumour angiogenesis. Hence, we investigated the potential effects of [Pt(O,O'-acac)(γ-acac)(DMS)] ([Pt(DMS)]), a new platinum drug for non-genomic targets, on human renal carcinoma and compared them with those of the well-established anticancer drug, cisplatin.
  
  
  
  Tumour growth, tumour cell proliferation and microvessel density were investigated in a xenograft model of renal cell carcinoma, developed by injecting Caki-1 cells into BALB/c nude mice. The antiangiogenic potential of compounds was also investigated using HUVECs.
  
  
  
  Treatment of the Caki-1 cells with cisplatin or [Pt(DMS)] resulted in a dose-dependent inhibition of cell survival, but the cytotoxicity of [Pt(DMS)] was approximately fivefold greater than that of cisplatin. [Pt(DMS)] was much more effective than cisplatin at inhibiting tumour growth, proliferation and angiogenesis in vivo, as well as migration, tube formation and MMP1, MMP2 and MMP9 secretion of endothelial cells in vitro. Whereas, cisplatin exerted a greater cytotoxic effect on HUVECs, but did not affect tube formation or the migration of endothelial cells. In addition, treatment of the xenograft mice with [Pt(DMS)] decreased VEGF, MMP1 and MMP2 expressions in tumours.
  
  
  
  The antiangiogenic and antitumour activities of [Pt(DMS)] provide a solid starting point for its validation as a suitable candidate for further pharmacological testing.
authors.affiliation: Laboratory of Cell Pathology, Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Muscella
authors.affiliation: Neuropathology Unit, Institute of Experimental Neurology and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Vetrugno
authors.affiliation: Laboratory of Neurobiology of Movement Disorders, Department of Molecular Pathology, I.R.C.C.S. Neuromed, Pozzilli, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Biagioni
authors.affiliation: Laboratory of Nutrigenomics and Vascular Biology, Institute of Clinical Physiology, National Research Council, Lecce, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Calabriso
authors.affiliation: Laboratory of Neurobiology of Movement Disorders, Department of Molecular Pathology, I.R.C.C.S. Neuromed, Pozzilli, Italy.
authors.forename: M T
authors.initials: MT
authors.lastname: Calierno
authors.affiliation: Laboratory of Neurobiology of Movement Disorders, Department of Molecular Pathology, I.R.C.C.S. Neuromed, Pozzilli, Italy.|Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Fornai
authors.affiliation: Laboratory of Inorganic Chemistry, Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Italy.
authors.forename: S A
authors.initials: SA
authors.lastname: De Pascali
authors.affiliation: Laboratory of Cell Physiology, Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Marsigliante
authors.affiliation: Laboratory of Inorganic Chemistry, Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Italy.
authors.forename: F P
authors.initials: FP
authors.lastname: Fanizzi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C527556:Pt(O,O'-acac)(gamma-acac)(DMS)