Standardized Punica Granatum Pericarp Extract, Suppresses Tumor Proliferation and Angiogenesis in a Mouse Model of Melanoma: Possible Involvement of PPARα and PPARγ Pathways

Melanoma is a challenging disease to treat. punica granatum l. has a potential anticancer effect. this study determined the antiproliferative and antiangiogenic potential of the extract from pomegranate pericarp (ppe) in melanoma. melanoma cells (1 × 106) were injected to c57bl6 mice subcutaneously. on 8th day, mice were randomly divided into 9 groups. group 1 was considered as control and received distilled water. groups 2 to 5 received 50, 100, 200 or 400 mg/kg of standardized ppe, orally. group 6 received 400 mg/kg ppe and ppar-γ antagonist (t0070907, 5 mg/kg/day). group 7 received 400 mg/kg ppe and ppar-α antagonist (gw6471, 10 mg/kg/day). groups 8 and 9 received ppar antagonists alone. on the 16th day, mice were euthanized and the tumor samples were analyzed by immunohistochemistry staining for ki-67 and cd31. vascular endothelial growth factor (vegf) plasma level was determined by elisa. ppe at the doses of 50, 100, 200, and 400 mg/kg decreased tumor weight to 1.28, 1.03, 0.82, and 0.58 g, respectively, in comparison with 1.46 g in control group. tumor volume reduced to 2.1, 1.7, 1.35 and 0.95 cm3 at the mentioned doses, in comparison with 2.4 cm3 in control group (p < 0.05 for all groups). vegf, ki-67 and cd31 were decreased dose dependently in the treatment groups (p < 0.05). pparα and pparγ antagonists significantly reduced the extract effects (p < 0.05). it was concluded that ppe may have a potential implication in melanoma treatment through activation of pparα and pparγ receptors.