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Pomegranate Polyphenols Suppress Colorectal Aberrant Crypt Foci (ACF) and Inflammation: Possible role of miR126 in vitro and in vivo
Author(s) -
Banerjee Nivedita,
Kim Hyemee,
Talcott Stephen,
Talcott Susanne U Mertens
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.248.5
Subject(s) - in vivo , pi3k/akt/mtor pathway , cancer research , microrna , chemistry , protein kinase b , downregulation and upregulation , aberrant crypt foci , cell growth , in vitro , microbiology and biotechnology , antagomir , apoptosis , colorectal cancer , biology , cancer , biochemistry , genetics , colonic disease , gene
The anti‐tumorigenic efficacy of polyphenols ellagitannins and anthocyanins extracted from pomegranate has been extensively studied in various cancer models. The objective of this study was to investigate the role of post‐transcriptional regulation of apoptotic and inflammatory biomarkers by specific microRNAs treated with pomegranate polyphenols (PP). mRNA, microRNA expression were measured by RT‐PCR, protein by western blotting and multiplex bead assay. In vivo studies were performed with Sprague Dawley rats. PP juice suppressed the number of high multiplicity aberrant crypts foci (HMACF >; 4 ACF) by 42% (P<0.05) and lowered Ki67 antigen. Cell proliferation was also inhibited by PP (5–25 μg/mL) in colon cancer cells HT‐29. In vitro and vivo results were accompanied by a downregulation of expression including NF‐κB, inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2), vascular adhesion molecule‐1 (VCAM‐1), insulin growth factor (IGF) and PI3K/Akt/mTOR signaling pathways. miRNA 126 is frequently lost in colon cancer and targets VCAM‐1 and PI3K. PP increased miR126 expression. In vitro, the involvement of miR‐126 was confirmed using the antagomir for miR‐126, where PP reversed the effects of the antagomir. In summary Pg inhibited HT29 cell proliferation, suppressed the number of HMACF formation and colon tumorgenesis where microRNA 126‐regulated pathways seem to be involved. Grant Funding Source : Vegetable and Fruit Improvement Center, Texas AandM University