title: Cytotoxicity and antiangiogenic activity of grandisin.
abstract: OBJECTIVE
  The antitumoural properties of grandisin, a tetrahydrofuran neolignan from Piper solmsianum, were investigated by in-vitro and in-vivo assays using the Ehrlich ascites tumoural (EAT) model.
  
  
  METHODS
  Viability of the tumour cells was evaluated by Trypan blue exclusion and MTT methods, after incubation with grandisin (0.017-2.3 microm). The effects of grandisin on the activity of caspase-3, -6, -8, and -9 were also investigated using colorimetric protease kits. In-vivo studies were performed in EAT-bearing mice treated intraperitoneally with 2.5, 5 or 10 mg/kg grandisin for 10 days.
  
  
  RESULTS
  Grandisin inhibited the growth of EAT cells, by both methods, with IC50 values less than 0.25 microm. The results showed that the activity of all the caspases studied increased in grandisin-treated cells, when compared with control, non-treated cells. Administering grandisin to EAT-bearing mice increased survival of the animals, in a dose-dependent manner. Simultaneously, we detected a 66.35% reduction of intraperitoneal tumour cell burden in the animals treated with 10 mg/kg grandisin. Additionally, in these animals, the marked increase of vascular endothelial growth factor (VEGF) levels, induced by EAT development, was decreased with treatment with grandisin, resulting in a reduction of 32.1% of VEGF levels in the peritoneal washing supernatant, when compared with the control.
  
  
  CONCLUSIONS
  The results demonstrated that grandisin induced in-vitro cytotoxicity and antiangiogenic effects in mice while it acted against tumour evolution, prolonging host survival.
authors: Laboratório de Farmacologia e Toxicologia Celular, Faculdade de Farmácia, Universidade Federal de Goiás, Goiânia, Go, Brazil. marizecv@farmacia.ufg.br
authors: Marize C
authors: MC
authors: Valadares
authors: Isabel Crhistyna Teles
authors: IC
authors: de Carvalho
authors: Luiz
authors: L
authors: de Oliveira Junior
authors: Marcelo de Sousa
authors: Mde S
authors: Vieira
authors: Polyana Lopes
authors: PL
authors: Benfica
authors: Flávio Silva
authors: FS
authors: de Carvalho
authors: Lorenna Vieira Silva
authors: LV
authors: Andrade
authors: Eliana Martins
authors: EM
authors: Lima
authors: Massuo Jorge
authors: MJ
authors: Kato
mesh_terms: D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D020128:Inhibitory Concentration 50; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D008517:Phytotherapy; D031701:Piper / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D017705:Lignans; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; C074346:grandisin; D020169:Caspases