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.