Document Type: Research article
Applied Physiology Research Center, Cardiovascular Research Institute, Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran.
Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Department of pharmacology, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Pharmacognosy, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
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 peel (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.