Cytotoxicity and antiangiogenic activity of grandisin

• Published in: Journal of pharmacy and pharmacology 2009-12, Vol.61 (12), p.1709-1714
• Main Authors: Valadares, Marize C., De Carvalho, Isabel Crhistyna Teles, Junior, Luiz de Oliveira, De Sousa Vieira, Marcelo, Benfica, Polyana Lopes, De Carvalho, Flávio Silva, Andrade, Lorenna Vieira Silva, Lima, Eliana Martins, Kato, Massuo Jorge
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - isolation & purification; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Animals; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; antitumour; Carcinoma, Ehrlich Tumor - drug therapy; Caspases - metabolism; Cell Proliferation - drug effects; cytotoxicity; Dose-Response Relationship, Drug; Furans - isolation & purification; Furans - pharmacology; Furans - therapeutic use; grandisin; Inhibitory Concentration 50; Lignans - isolation & purification; Lignans - pharmacology; Lignans - therapeutic use; Male; Mice; Neoplasms, Experimental - drug therapy; Neovascularization, Pathologic - drug therapy; Phytotherapy; Piper - chemistry; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Plant Leaves; vascular endothelial growth factor; Vascular Endothelial Growth Factor A - blood
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1211/jpp.61.12.0017

Objectives 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 μM). 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. Key findings Grandisin inhibited the growth of EAT cells, by both methods, with IC50 values less than 0.25 μM. 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.