Article Text

other Versions

PDF
Cell kinetics and gene expression changes in colorectal cancer patients given resistant starch - A randomised controlled trial
  1. Shridhar S Dronamraju (mailshridhar{at}yahoo.com)
  1. North Tyneside General Hospital, North Shields, Tyne and Wear, United Kingdom
    1. Jonathan M Coxhead (j.m.coxhead{at}ncl.ac.uk)
    1. Human Nutrition Research Centre, Newcastle University, United Kingdom
      1. Seamus B Kelly (john.burn{at}ncl.ac.uk)
      1. North Tyneside General Hospital, North Shields, Tyne and Wear, United Kingdom
        1. John Burn (seamus.kelly{at}nhct.nhs.uk)
        1. Institute of Human Genetics, Newcastle University, United Kingdom
          1. John C Mathers (john.mathers{at}ncl.ac.uk)
          1. Human Nutrition Research Centre, Newcastle University, United Kingdom

            Abstract

            Objective: This study investigated the effects of oral supplementation with resistant starch (RS) on tumour cell and colonic mucosal cell kinetics and on gene expression in patients with colorectal cancer (CRC) and its potential role in colon cancer prevention.

            Methods: 65 patients with CRC were randomised to treatment with RS or ordinary starch (OS) and were given starch treatment for up to 4 weeks. Pre and post treatment biopsies were obtained from the tumour and colonic mucosa and the effects of the starch treatment on cell proliferation and expression of cell cycle regulatory genes CDK4 and GADD45A were investigated.

            Results: The proportion of mitotic cells in the top half of the colonic crypt was significantly lower following RS treatment [3.1(SEM 1.5)] when compared with OS treatment [13.7 (SEM 3.2)] (P=0.028). However, there was no effect of RS treatment on crypt dimensions or on tumour cell proliferation index. Following RS treatment, CDK4 expression in tumours [0.88 (SEM 0.15)] was two fold higher than that in the OS group [0.37 (SEM 0.16)] (P=0.02). The expression of GADD45A, which was down regulated in tumour tissue, was up regulated significantly (P=0.048) following RS treatment [1.41 (SEM 0.26)] compared with OS treatment [0.56 (SEM 0.3)].

            Conclusions: Cell proliferation in the upper part of colonic crypts is a pre-malignant marker and its reduction by RS supplementation is consistent with an anti-neoplastic action of this food component. Differential expression of the key cell cycle regulatory genes may contribute to the molecular mechanisms underlying these anti-neoplastic effects of RS.

            Statistics from Altmetric.com

            Request permissions

            If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

            Linked Articles