Oral feeding of pomegranate fruit extract inhibits early biomarkers of UVB radiation-induced carcinogenesis in SKH-1 hairless mouse epidermis

Photochem Photobiol. Nov-Dec 2010;86(6):1318-26. doi: 10.1111/j.1751-1097.2010.00815.x. Epub 2010 Oct 14.

Abstract

Pomegranate from the plant Punica granatum L. possesses strong antioxidant and anti-inflammatory properties. Recently, we have demonstrated that treatment of normal human epidermal keratinocytes with pomegranate fruit extract (PFE) inhibited UVB-mediated activation of nuclear factor kappa B (NF-κB) and mitogen activated protein kinases pathways. Here, we evaluated the effect of PFE on early biomarkers of photocarcinogenesis employing SKH-1 hairless mice. PFE was provided in drinking water (0.2%, wt/vol) to SKH-1 hairless mice for 14 days before a single UVB (180 mJ cm(-2)) irradiation. We found that oral feeding of PFE inhibited UVB-induced: (1) skin edema; (2) hyperplasia; (3) infiltration of leukocytes; (4) lipid peroxidation; (5) hydrogen peroxide generation; (6) ornithine decarboxylase (ODC) activity; and (7) ODC, cyclooxygenase-2 and proliferating cell nuclear antigen protein expression. Oral feeding of PFE enhanced repair of UVB-mediated formation of cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). Importantly, PFE treatment further enhanced UVB-mediated increase in tumor suppressor p53 and cyclin kinase inhibitor p21. Furthermore, oral feeding of PFE inhibited UVB-mediated: (1) nuclear translocation of NF-κB; (2) activation of IKKα; and (3) phosphorylation and degradation of IκBα. Taken together, we provide evidence that oral feeding of PFE to mice affords substantial protection from the adverse effects of UVB radiation via modulation in early biomarkers of photocarcinogenesis and provide suggestion for its photochemopreventive potential.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Animals
  • Anticarcinogenic Agents / administration & dosage
  • Biomarkers, Tumor / metabolism
  • Cyclooxygenase 2 / metabolism
  • DNA Repair / drug effects
  • Female
  • Fruit
  • Humans
  • Hydrogen Peroxide / metabolism
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / radiation effects
  • Lythraceae*
  • Mice
  • Mice, Hairless
  • Neoplasms, Radiation-Induced / prevention & control*
  • Ornithine Decarboxylase / metabolism
  • Ornithine Decarboxylase Inhibitors
  • Plant Extracts / administration & dosage
  • Proliferating Cell Nuclear Antigen / metabolism
  • Skin / drug effects
  • Skin / metabolism
  • Skin / pathology
  • Skin / radiation effects
  • Skin Neoplasms / prevention & control*
  • Ultraviolet Rays / adverse effects

Substances

  • Anticarcinogenic Agents
  • Biomarkers, Tumor
  • Ornithine Decarboxylase Inhibitors
  • Plant Extracts
  • Proliferating Cell Nuclear Antigen
  • Hydrogen Peroxide
  • Cyclooxygenase 2
  • Ornithine Decarboxylase