title: Plum polyphenols inhibit colorectal aberrant crypt foci formation in rats: potential role of the miR-143/protein kinase B/mammalian target of rapamycin axis.
abstract: The nutritional prevention of aberrant crypt foci by polyphenols may be a crucial step to dietary cancer prevention. The objective of this study was to determine the underlying mechanisms that contribute to the anti-inflammatory and antitumorigenic properties of plum (Prunus salicina L.) polyphenols, including chlorogenic acid and neochlorogenic acid, in azoxymethane (AOM)-treated rats. The hypothesis was that plum polyphenolics suppress AOM-induced aberrant crypt foci formation through alterations in the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and relative micro-RNA expressions. Sprague-Dawley rats (n=10/group) received plum beverage (1346mg gallic acid equivalents/L) or a control beverage ad libitum for 10 weeks with subcutaneous injections of AOM (15mg/kg) at weeks 2 and 3. Results show that the consumption of the plum beverage decreased the number of dysplastic aberrant crypt foci by 48% (P<.05) and lowered proliferation of mucosal cells by 24% (P<.05). The plum beverage decreased the activity of glutathione peroxidase, superoxide dismutase, and catalase in mucosal scrapings, as well as the superoxide dismutase activity in serum. The results were accompanied by a down-regulation of proinflammatory enzymes nuclear factor κB, nitric oxide synthase, cyclooxygenase-2, and vascular cell adhesion molecule 1 messenger RNA. Plum inhibited the expression of AKT and mTOR messenger RNA, phosphorylated AKT, mTOR, and hypoxia-inducible factor-1α protein levels, and the ratio of the phosphorylated/total protein expression of mTOR. Also, the plum beverage increased the expression of miR-143, which is involved in the regulation of AKT. These results suggest that plum polyphenols may exhibit a chemopreventive potential against colon carcinogenesis by impacting the AKT/mTOR pathway and miR-143.
authors.affiliation: Interdisciplinary Program of Toxicology, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Nivedita
authors.initials: N
authors.lastname: Banerjee
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Hyemee
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Talcott
authors.affiliation: Interdisciplinary Program of Toxicology, Texas A&M University, College Station, TX 77843, USA; Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Turner
authors.affiliation: Department of Horticulture, Texas A&M University, College Station, TX 77843, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Byrne
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA; Department of Veterinary Physiology & Pharmacology, Texas A&M University, College Station, TX 77843, USA. Electronic address: smtalcott@tamu.edu.
authors.forename: Susanne U
authors.initials: SU
authors.lastname: Mertens-Talcott
mesh_terms: D058739:Aberrant Crypt Foci / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001397:Azoxymethane; D049109:Cell Proliferation; D002726:Chlorogenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000517:prevention & control; D004032:Diet; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols / Q000494:pharmacology* / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000068242:Prunus domestica / Q000737:chemistry*; D011801:Quinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D016588:Anticarcinogenic Agents; D001397:Azoxymethane; D002726:Chlorogenic Acid; D018836:Inflammation Mediators; D035683:MicroRNAs; D010936:Plant Extracts; D059808:Polyphenols; D051057:Proto-Oncogene Proteins c-akt; D011801:Quinic Acid; D058570:TOR Serine-Threonine Kinases; C569508:MIRN143 microRNA, rat; C546845:mTOR protein, rat; C473200:5-caffeoylquinic acid
keywords: Chlorogenic acid; Colon cancer; Inflammation; Plum; Rat; mTOR; miR-143