scholarly journals Effects of Total Western Diet and Wheat Class and Fraction on Preneoplastic Colon Cancer Risk

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 262-262
Author(s):  
Allison Bailey ◽  
Daniel Gallaher ◽  
Senay Simsek

Abstract Objectives Colon cancer (CC) is a leading cause of cancer-related deaths worldwide and is particularly prevalent among persons consuming a Western-style diet. Red wheat, compared to white wheat, may reduce CC risk, as measured by reductions in colonic preneoplastic lesions (aberrant crypt foci; ACF). Rodent studies typically use a purified diet (AIN-93G) as the background diet, but due to its optimal nutritional composition, it may mask some effects of chemopreventive bioactives. The Total Western Diet (TWD), matched to the 50th percentile of US diets using NHANES data, has greater translational integrity to humans. This study aims to elucidate effects of background diet (AIN-93G vs TWD), wheat class (red vs white), and wheat fraction (whole vs refined vs testa layer) when fed during the post-initiation period. Methods Male Wistar rats (n = 83) were injected with the colon-specific carcinogen 1,2-dimethylhydrazine (twice, one week apart) to induce ACF. Five days after final injection, diets containing either AIN-93G or TWD background and various fractions of red and white wheat were fed for 10 weeks. Results No statistically significant differences in ACF number were found due to background diet. However, a statistically significant decrease in ACF was found in rats fed the TWD + whole red wheat (RW) relative to the TWD and the AIN-93G + refined red wheat diets. The short-chain fatty acid (SCFA) butyrate may act as a histone deacetylase to prevent CC. TWD + RW significantly increased total SCFAs as well as total butyrate compared to all other groups. TWD had significantly decreased total SCFAs and total butyrate compared to AIN-93G. Preliminary immunohistochemical results show that neither beta-catenin (part of the Wnt signaling pathway frequently dysregulated in CC) nor doublecortin-like kinase 1 (DCLK1; a putative cancer stem cell marker) staining of ACF significantly differ between TWD and TWD + RW. Conclusions The butyrate amount in cecal contents did not correlate with the staining intensity within ACF for beta-catenin or DCLK1 biomarkers, which does not support a role for high total butyrate reducing the risk of CC. Red wheat, when fed as part of the TWD, may reduce CC risk. Funding Sources Healthy Foods, Healthy Lives Institute, University of Minnesota.

2019 ◽  
Vol 149 (2) ◽  
pp. 249-257 ◽  
Author(s):  
Sangyub Kim ◽  
Sabrina P Trudo ◽  
Daniel D Gallaher

ABSTRACT Background 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 male Wistar 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 vegetable-containing 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 vegetable-containing groups compared to the basal group. Bioinformatic analysis of these expression changes in miRNA predicted a change in WNT/β-catenin signaling, indicating downregulation of β-catenin in the vegetable-fed groups. Consistent with this bioinformatics analysis, β-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.


2013 ◽  
Vol 33 (2) ◽  
pp. 148-163 ◽  
Author(s):  
OO Hamiza ◽  
MU Rehman ◽  
R Khan ◽  
M Tahir ◽  
AQ Khan ◽  
...  

Chemoprevention opens new window in the prevention of all types of cancers including colon cancer. Aloin, an anthracycline in plant pigment, can be utilized as a protective agent in cancer induction. In the present study, we have evaluated the chemopreventive efficacy of aloin against 1,2-dimethylhydrazine (DMH)-induced preneoplastic lesions in the colon of Wistar rats. DMH-induced aberrant crypt foci (ACF) and mucin-depleted foci (MDF) have been used as biomarkers of colon cancer. Efficacy of aloin against the colon toxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, lipid peroxidation, ACF, MDF, histopathological changes, and expression levels of molecular markers of inflammation and tumor promotion. Aloin pretreatment ameliorates the damaging effects induced by DMH through a protective mechanism that involved reduction in increased oxidative stress enzymes ( p < 0.001), ACF, MDF, cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6, proliferating cell nuclear antigen protein expression, and tumor necrosis factor-α ( p < 0.001) release. From the results, it could be concluded that aloin clearly protects against chemically induced colon toxicity and acts reasonably by inducing antioxidant level, anti-inflammatory and antiproliferative markers.


ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Yu-Wei Guo ◽  
Yue-Hwa Chen ◽  
Wan-Chun Chiu ◽  
Hsiang Liao ◽  
Shyh-Hsiang Lin

Objective. The effect of extracted crude soybean saponins on preneoplastic lesions, aberrant crypt foci (ACF), and the related mechanism were investigated. Research Methods and Procedures. Rats were assigned into five groups according to different doses of extracted crude soybean saponins and received 1,2-dimethylhydrazine (DMH) injection in week 5. In week 15, all rats were sacrificed. The number of ACFs, the cyclooxygenase-2 (COX-2) protein expression, the level of prostaglandins E2 (PGE2), and the activity of β-glucuronidase were examined. Results. Results revealed that the consumption of extracted crude soybean saponins decreased the number of ACFs and the activity of β-glucuronidase in rats, while the expression of COX-2 protein and PGE2 level were not affected. Conclusions. Soybean saponins were effective in inhibiting colon cancer by downregulating the activity of β-glucuronidase in colonic mucosa but not the COX-2 protein expression and PGE2 level.


Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2168 ◽  
Author(s):  
Chih-Wei Lee ◽  
Hong-Jhang Chen ◽  
Gui-Ru Xie ◽  
Chun-Kuang Shih

Djulis is a cereal crop rich in polyphenols and dietary fiber that may have nutraceutical activity to prevent colon cancer. This study was designed to examine the preventive effect of djulis on colon carcinogenesis in rats treated with 1,2-dimethylhydrazine (DMH). Rats were fed different AIN-93G-based diets: groups N and DMH were fed AIN-93G diet and groups LD, MD, and HD were fed AIN-93G diet containing 5, 10, and 20% djulis, respectively. All rats except for group N were injected with DMH to induce colon carcinogenesis. After 10 weeks, rats were sacrificed and colon and liver tissues were collected for analysis. The results showed that djulis-treated rats had significantly lower numbers of colonic preneoplastic lesions, aberrant crypt foci (ACF), sialomucin-producing (SIM)-ACF, and mucin-depleted foci. Djulis treatment increased superoxide dismutase and catalase activities in colon and liver. Djulis also reduced p53, Bcl-2, and proliferating cell nuclear antigen expressions and increased Bax and caspase-9 expressions. Besides, phenolic compounds and flavonoids were found rich in djulis. These results demonstrate the chemopreventive effect of djulis on carcinogen-induced colon carcinogenesis via regulating antioxidative and apoptotic pathways in rats. Djulis may have the potential to be developed as a valuable cereal product for chemoprevention of colon cancer.


Author(s):  
Ade Arsianti Arsianti ◽  
Anindini Winda Amalia ◽  
Kusmardi Suid ◽  
Berna Elya

Objective: Colon cancer is a major public health problem. Soybean has demonstrated chemopreventive and anti-cancer. Here, we have investigated the effect of a standardized seed and soybean meal extract with content of  lunasin, here named  GE and SE. They are botanical drug substance in experimental models of colon cancer in vivo.Methods:The effect of  GE and SEwere examined onthe preneoplastic lesions (aberrant crypt foci), polyps and tumours induced by the carcinogenic agentazoxymethane (AOM) (10 mg/kg) and dextran sodium sulfate (DSS) 2%  as well as in a xenograft model of colon cancer in mice.Results:.GE and SE increased apoptosis (p = 0,001). GE (150 mg/kg) has the highest impact level of apoptosis (p = 0,009). GE and  SE decreased dysplasia (p = 0,024). GE (200 mg/kg) has the highest impact level of dysplasia (p = 0,002) and SE (200 mg/kg) has the second impact level of dysplasia (p = 0,003).Conclusions: GE and SE inhibition of colon carsinogenesis with incrase level of apoptosis and decrease level of dysplasiaKeyword: soybean, lunasin, colon cancer, azoxymethane, dextran sodium sulfate, apoptosis, dysplasia


2020 ◽  
Vol 26 (15) ◽  
pp. 1729-1741 ◽  
Author(s):  
Seyed H. Shahcheraghi ◽  
Venant Tchokonte-Nana ◽  
Marzieh Lotfi ◽  
Malihe Lotfi ◽  
Ahmad Ghorbani ◽  
...  

: Glioblastoma (GBM) is the most common and malignant astrocytic glioma, accounting for about 90% of all brain tumors with poor prognosis. Despite recent advances in understanding molecular mechanisms of oncogenesis and the improved neuroimaging technologies, surgery, and adjuvant treatments, the clinical prognosis of patients with GBM remains persistently unfavorable. The signaling pathways and the regulation of growth factors of glioblastoma cells are very abnormal. The various signaling pathways have been suggested to be involved in cellular proliferation, invasion, and glioma metastasis. The Wnt signaling pathway with its pleiotropic functions in neurogenesis and stem cell proliferation is implicated in various human cancers, including glioma. In addition, the PI3K/Akt/mTOR pathway is closely related to growth, metabolism, survival, angiogenesis, autophagy, and chemotherapy resistance of GBM. Understanding the mechanisms of GBM’s invasion, represented by invasion and migration, is an important tool in designing effective therapeutic interventions. This review will investigate two main signaling pathways in GBM: PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways.


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