Apiaceous and Cruciferous Vegetables Fed during the Post-Initiation Stage Reduce Colon Cancer Risk Markers in Rats

Sangyub Kim, Sabrina P. Trudo, Dan D Gallaher

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)249-257
Number of pages9
JournalJournal of Nutrition
Volume149
Issue number2
DOIs
StatePublished - Feb 1 2019

Fingerprint

Aberrant Crypt Foci
Vegetables
Colonic Neoplasms
MicroRNAs
Catenins
Diet
Computational Biology
1,2-Dimethylhydrazine
Neoplastic Stem Cells
Colon
Carcinogenesis
Phosphotransferases
Down-Regulation
Fats
Carbohydrates
Proteins

Keywords

  • apiaceous vegetables
  • cancer stem cells
  • colon cancer
  • cruciferous vegetables
  • miRNA

Cite this

Apiaceous and Cruciferous Vegetables Fed during the Post-Initiation Stage Reduce Colon Cancer Risk Markers in Rats. / Kim, Sangyub; Trudo, Sabrina P.; Gallaher, Dan D.

In: Journal of Nutrition, Vol. 149, No. 2, 01.02.2019, p. 249-257.

Research output: Contribution to journalArticle

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title = "Apiaceous and Cruciferous Vegetables Fed during the Post-Initiation Stage Reduce Colon Cancer Risk Markers in Rats",
abstract = "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.",
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N2 - 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.

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