Vegetable consumption reduces colon cancer risk when fed in the initiation stage of carcinogenesis; however, the effect of vegetable consumption during the post-initiation stage has rarely been examined. Objective: We investigated the chemopreventive effects of feeding apiaceous and cruciferous vegetables on colon cancer risk in the post-initiation stage. Methods: Thirty maleWistar rats (~5 wk, 92 g) were subcutaneously injected with 1,2-dimethylhydrazine 1 time/wk for 2 wk. One week after the last dose, rats were randomly assigned to 3 groups: the basal diet, an apiaceous vegetablecontaining diet (API; 21% fresh wt/wt), or a cruciferous vegetable-containing diet (CRU; 21% fresh wt/wt). All diets contained ~20% protein, 7% fat, and 63% digestible carbohydrate. Experimental diets were fed for 10 wk, after which colons were harvested. Results: CRU reduced aberrant crypt foci (ACF) number compared to the basal group (P = 0.014) and API (P = 0.013), whereas API decreased the proportion of dysplastic ACF relative to the basal group (P < 0.05). Both CRU and API reduced doublecortin-like kinase 1-positive marker expression relative to basal by 57.9% (P = 0.009) and 51.4% (P < 0.02). The numbers of CD44-positive ACF did not differ between the groups. We identified 14 differentially expressed microRNAs (miRNAs). Of these, expression of 6 miRNAs were greater or tended to be greater (P = 0.10) in one or both vegetablecontaining groups compared to the basal group. Bioinformatic analysis of these expression changes in miRNA predicted a change in WNT/B-catenin signaling, indicating downregulation of B-catenin in the vegetable-fed groups. Consistent with this bioinformatics analysis, B-catenin-accumulated ACF were decreased in CRU (93.1%, P = 0.012), but not in API (54.4%, P = 0.125), compared to the basal group. Conclusion: Both apiaceous and cruciferous vegetables, fed post-initiation, reduce colonic preneoplastic lesions as well as cancer stem cell marker expression in rats, possibly by suppressing oncogenic signaling through changes in miRNA expression. J Nutr 2019;149:249-257.
Bibliographical noteFunding Information:
Supported by the Healthy Foods Healthy Lives Institute, University of Minnesota, and the Minnesota Agricultural Station. Author disclosures: SK, SPT, and DDG, no conflicts of interest. Supplemental Tables 1–7 and Supplemental Figures 1–4 are available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/jn/. Current address for SK: Department of Pharmacology, Pennsylvania State College of Medicine, Hershey, PA. Address correspondence to DDG (e-mail: email@example.com). Abbreviations used: AC, aberrant crypt; ACF, aberrant crypt foci; API, apiaceous vegetable–containing diet; CRU, cruciferous vegetable–containing diet; CSC, cancer stem cell; DCLK1, doublecortin-like kinase 1; ERK, extracellular signal-regulated kinase; IPA, Ingenuity Pathway Analysis software; MDF, mucin-depleted foci; miRNA, micro RNA; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; RIN, RNA integrity number; SiM, sialomucin-expressing aberrant crypt foci.
© 2019 American Society for Nutrition. All rights reserved.
- apiaceous vegetables
- cancer stem cells
- colon cancer
- cruciferous vegetables