The Inhibitory Effect of Hydroalcoholic Extract of Black Punica Granatum Pericarp on the Number of Endothelial Progenitor Cells (EPCs) in Melanoma through Peroxisome Proliferator-Activated Receptor-α and γ (PPAR-α and γ) Pathways in C57BL6 Mice

Document Type : Original Article (s)

Authors

1 Applied Physiology Research Center AND Department of Physiology, School of Medicine AND Pharmaceutical Sciences Research Center, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

2 Applied Physiology Research Center AND Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Associate Professor, Applied Physiology Research Center AND Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Endothelial progenitor cells (EPCs) play an important role in tumor growth and angiogenesis. Punica granatum, from Punicaceae family, has demonstrated anticancer effects in different types of cancers. This study aimed to determine the effect of hydroalcoholic extract of pomegranate peel on the number of EPCs in mouse model of melanoma and also to determine its mechanism of action.Methods: The hydroalcoholic extract of black pomegranate pericarp was prepared using 70% ethanol containing 1% acetic acid. 1 × 106 B16F10 melanoma cells were injected to each of 88 C57BL6 male mice weighing 25 g on the day 0, subcutaneously (s.c). On 7th day, mice were randomly divided into 11 groups of 8 animals. The first group (control) received distilled water. Groups second to fifth from the seventh day of the study received 50, 100, 200 and 400 mg/kg of standardized polyphenon E (PPE) via gavage. The sixth group received PPE and peroxisome proliferator-activated receptor gamma (PPAR-γ) antagonist (5 mg/kg/day) intraperitoneally. The seventh group received PPE and PPAR-α antagonist (10 mg/kg/day) intraperitoneally. Eighth and ninth groups received fenofibrate (100 mg/kg) and rosiglitazone (100 mg/kg) as agonists of PPAR-α and PPAR-γ, respectively, via gavage. Tenth and eleventh groups received PPAR antagonists, merely. On 16th day, mice were euthanized and were bled through heart puncture for EPC enumeration via flow cytometry. In flow cytometry, CD34+/VEGFR2+ cells were enumerated.Findings: PPE dose-dependently decreased the number of EPCs (P < 0.05). Number of EPCs in the groups which received fenofibrate and rosiglitazone was less than the group that received the highest dose of PPE (P < 0.05). Moreover, EPCs in the groups which received both PPAR antagonists and PPE, was more than the group which received PPE (P < 0.01).Conclusion: In conclusion, we demonstrated that PPE is effective in reducing the number of EPCs and part of this effect is through modulation of PPAR pathway.

Keywords

References

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Journal of Isfahan Medical School
Volume 33, Issue 334 - Serial Number 334
March and April 2015
Pages 685-693

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History

  • Receive Date: 26 February 2015
  • Revise Date:
  • Accept Date: 06 April 2022

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