Punica granatum suppresses colon cancer through downregulation of Wnt/β-Catenin in rat model

Abstract

This study aims to elucidate the beneficial effect of Punica granatum L., Lythraceae (pomegranate) peel extract in the management of colon cancer induced intrarectally with N-methylnitrosourea. Adult male Sprague-Dawley rats were administered N-methylnitrosourea (2 mg in 0.5 ml water/rat) intrarectally three times/week for five weeks to induce colorectal cancer, followed by treatment with either 5-fluorouracil (12.5 mg/kg, i.p.) or Punica peel extract (2.25 or 4.5 g/kg, p.o.). Developed tumor elevated plasma TGF-β, and Bcl2, serum epidermal growth factor, carcinoembryonic antigen, colon cancer specific antigens, and matrix metalloproteinase-7. Besides, immune-histochemical studies revealed an increase in COX-2, cyclin D1 and survivin content, as well as upregulation of the expression of colonic β-Catenin, K-ras and C-myc genes. These results were further supported by the histological findings. Punica peel extract-treated rats, particularly those treated with a high dose, exhibited a marked reduction in the aforementioned parameters and improved the histological organization of the colon tissue. These alterations were consistent with those mediated through 5-fluorouracil. The present study encourages the use of P. granatum L. against colon cancer. Because Punica peel extract promotes apoptosis, mitigates inflammation and suppresses tumor cell proliferation in vivo, the potential mechanism underlying these activities might depend on the inhibition of the Wnt/β-Catenin signaling pathway.

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Correspondence to Mohamed B. Shalaby.

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Authors contributions

MBS (PhD student) contributed in collecting and running the laboratory work. HHA supervised the laboratory work. HHA, HSE and NFA contributed in writing the manuscript. HHA and HSE contributed in designing the study, critical analysis of data, supervised the laboratory work. EAKH contributed to molecular and HPLC analysis. All the authors have read the final manuscript and approved the submission.

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Ahmed, H.H., El-Abhar, H.S., Hassanin, E.A.K. et al. Punica granatum suppresses colon cancer through downregulation of Wnt/β-Catenin in rat model. Rev. Bras. Farmacogn. 27, 627–635 (2017). https://doi.org/10.1016/j.bjp.2017.05.010

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Keywords

  • Colon cancer
  • Pomegranate
  • Wnt/β-Catenin
  • Inflammation
  • Proliferation
  • Apoptosis