Apiaceous and cruciferous vegetables fed in the post‐initiation stage reduce colonic precancerous lesions and the cancer stem cell marker DCLK1, and alter the miRNA expression profile in 1,2‐dimethylhydrazine‐treated rats
Authors: Kim Sangyub , Trudo Sabrina P , Gallaher Daniel D 
Published: November 2023

Previously, we found that cruciferous vegetables reduced colonic precancerous lesions (aberrant crypt foci, ACF) in rats when fed during the initiation stage and through the post‐initiation stage of colon cancer. Further, we have found that apiaceous vegetables fed prior to carcinogen administration reduced colonic DNA adduct formation in rats. However, neither of these classes of vegetables have been examined for chemopreventive effects on early biomarkers of colon cancer when fed only in the post‐initiation stage. The primary aim of our study was to determine the effects of apiaceous and cruciferous vegetables on the number of total ACF, dysplastic ACF [sialomucin‐expressing ACF (SIM) and mucin‐depleted ACF (MDF)], and cancer stem cells (CSCs) in the post‐initiation stage of colon carcinogenesis. The second goal of our study was to investigate whether these vegetables altered the miRNA expression profile in the colon in a manner consistent with a lower risk of colon cancer, as the miRNA profile is commonly dysregulated in cancer. Rats were adapted to a vegetable‐free basal diet for 1 wk, then administered dimethylhydrazine once a wk for 2 wks. One week after the last dose, rats were divided into 3 groups. One group remained on the basal diet, one group was fed a cruciferous vegetable‐based diet (CRU), and one group was fed an apiaceous vegetable‐based diet (API). Vegetable‐based diets contained 21% vegetables on a wet wt basis. After 10 wks, colons were harvested. ACF number was 14.2% and 18.4% lower in the CRU group compared to the basal and API groups, respectively (p<0.02). Interestingly, the proportion of SIM and MDF (SIM+MDF/total ACF), which are dysplastic ACF suggested to be more tumorigenic than hyperplastic ACF, was 19.6% lower in API group relative to the basal group (p=0.047). CSCs are suggested to be the cells of origin in cancer development, and are believed to be a cause of cancer relapse and chemotherapy resistance. The inflammation‐related CSC marker (doublecortin‐like kinase 1; DCLK1) was measured in ACF by immunohistochemistry. Both CRU and API groups had 50.0% and 41.5% fewer DCLK1‐positive CSCs in ACF compared to the basal group, respectively (p<0.03). Moreover, miRNA expression profiling of the colons indicated that feeding rats cruciferous vegetables modulated the expression of inflammation‐related miRNAs (e.g., miR‐146 family and 196b), suggesting an anti‐inflammatory effect of cruciferous vegetables on ACF formation. Rats fed the apiaceous vegetable diet had greater counts of the stemness‐inhibiting miRNAs miR‐183, ‐200 family, and ‐203. This could potentially suppress the formation of DCLK1‐positive CSCs, thus reducing the risk of progression of ACF to MDF. Therefore, when fed only in the post‐initiation stage, both apiaceous and cruciferous vegetables may reduce the risk of colon carcinogenesis at an early stage, but the chemopreventive mechanisms may differ.

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Sponsored by the Healthy Foods, Healthy Lives Institute of the University of Minnesota.