Pomegranate polyphenolics suppressed azoxymethane-induced colorectal aberrant crypt foci and inflammation: Possible role of miR-126/VCAM-1 and miR-126/PI3K/ AKT/mTOR | Academic Article individual record
abstract

The antitumorigenic activities of polyphenols such as ellagitannins and anthocyanins in pomegranate (Punica granatum L.) have been previously studied where cytotoxic, anti-inflammatory and antioxidant effects were evident in various cancer models. The objective of this study was to investigate the role of miR-126/vascular cell adhesion molecule 1 (VCAM-1) and miR-126/phosphatidylinositol- 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) in pomegranate-mediated anti-inflammatory and anticarcinogenic effects in vivo and in vitro. Sprague-Dawley rats (n = 10 per group) received pomegranate juice (2504.74 mg gallic acid equivalents/l) or a polyphenol-free control beverage ad libitum for 10 weeks and were injected with azoxymethane (AOM) subcutaneously (15 mg/kg) at weeks 2 and 3. Consumption of pomegranate juice suppressed the number of aberrant crypt foci (ACF) and dysplastic ACF by 29 and 53.5% (P = 0.05 and 0.04), respectively, and significantly lowered proliferation of mucosa cells. Pomegranate juice significantly downregulated proinflammatory enzymes nitric oxide synthase and cyclooxygenase-2 messenger RNA (mRNA) and protein expression. In addition, it suppressed nuclear factor- κB and V CAM-1 mRNA and protein expression in AOM-treated rats. Pomegranate also inhibited phosphorylation of PI3K/AKT and mTOR expression and increased the expression of miR-126. The specific target and functions of miR-126 were investigated in HT-29 colon cancer cell lines. In vitro, the involvement of miR-126 was confirmed using the antagomiR for miR-126, where pomegranate reversed the effects of the antagomiR on the expression of miR-126, VCAM-1 and PI3K p85β. In summary, therapeutic potentials of pomegranate in colon tumorigenesis were due in part to targeting miR-126-regulated pathways, which contributes in the underlying anti-inflammatory mechanisms. © The Author 2013. Published by Oxford University Press.

author list (cited authors)
Banerjee, N., Kim, H., Talcott, S., & Mertens-Talcott, S.
publication date
2013
published in
keywords
  • Proto-Oncogene Proteins C-akt
  • MicroRNAs
  • Beverages
  • Male
  • Colorectal Neoplasms
  • Animals
  • Cell Proliferation
  • Rats
  • Cyclooxygenase 2
  • Cell Line, Tumor
  • Vascular Cell Adhesion Molecule-1
  • Anticarcinogenic Agents
  • Humans
  • Aberrant Crypt Foci
  • Inflammation
  • Rats, Sprague-Dawley
  • Polyphenols
  • Azoxymethane
  • Nitric Oxide Synthase Type II
  • HT29 Cells
  • Punicaceae
  • Phosphatidylinositol 3-kinase
  • TOR Serine-Threonine Kinases
altmetric score

0.5

citation count

68