scholarly journals Chemoprevention against colon cancer by dietary intake of sulforaphane

2019 ◽  
Vol 9 (6) ◽  
pp. 392
Author(s):  
Akinori Yanaka ◽  
Hideo Suzuki ◽  
Michihiro Mutoh ◽  
Toshiro Kamoshida ◽  
Nobushige Kakinoki ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Antioxidant Enzymes ◽  
Dietary Intake ◽  
Tumor Cells ◽  
Intestinal Microbiota ◽  
Colonic Mucosa ◽  
Aberrant Crypt Foci ◽  
Chemical Carcinogen ◽  
Colonic Adenoma ◽  
Broccoli Sprouts

Background: Sulforaphane (SFN), a phytochemical compound, which belongs to isothiocyanates family found in abundance in broccoli sprouts, potently induces a variety of antioxidant enzymes via nrf2-keap1 mediated pathway, thereby protects cells from injury induced by various kinds of oxidative stresses. We have previously shown that SFN protects gastric mucosa from oxidative injury induced by H. pylori infection. SFN also down-regulates histone deacetylase (HDAC) activity, thereby induces apoptosis and inhibits proliferation of tumor cells in variety of tissues. On the other hand, colon cancer has been increasing in Japan. Since numerous epidemiological studies have shown that colon cancer is inversely associated with intake of anti-oxidant vegetables, we examined if dietary SGS prevents colon tumorigenesis in mice, and in human subjects.Methods:  1. Effects of SFN on Colonic tumorigenesis in Mice Treated with Chemical Carcinogen: Effects of SFN on colonic tumorigenesis were examined in the ICR male mice, pretreated with a chemical carcinogen, azoxymethane (AOM) (15 mg/kg). The AOM-treated mice were fed for 8 weeks with or without sulforaphane glucosinolates (SGS: 2,200 ppm/kg/day), which is a precursor of SFN. Effects of SGS treatment on formation of the microscopic aberrant crypt foci (ACF), and the macroscopic tumors in colonic mucosa were evaluated. 2. Effects of SFN on formation of Colonic Aberrant Crypt Foci (ACF) in patients with colonic adenoma: Effects of intake of raw broccoli sprouts (BS), 50 g/day, which contains 220 mg SGS every other day, for 6 months on changes in the number of ACF in rectal mucosa was examined by colonoscopy in patients with colonic adenoma. 3. Effects of SFN on intestinal microbiota in human subjects:  Effects of dietary intake of raw broccoli sprouts (BS), 20 g/day, which contains 88 mg SGS every other day, for 2 weeks on intestinal microbiota in healthy volunteers was assessed by measuring composition of stool bacteria, using T-RFLP method. In human studies, alfalfa sprouts, which contains no SFN was used as a placebo control. Results: 1. Daily administration of SGS suppressed formation of microscopic ACF and macroscopic colonic tumors in the AOM-pretreated mice in vivo. 2. Intake of BS for 6 months tended to decrease the number of colonic ACF in patients with colonic adenoma. 3. Intake of BS for 2 weeks increased percentages of Bifidobacterium and Clostridium XVIa, which has been shown to enhance protection of colonic mucosa by increasing butyrate production in colonic lumen.Conclusions: 1. SFN affords chemoprotection against colonic cancer, presumably by up-regulating nrf2-dependent antioxidant enzymes in normal colonic epithelial cells, and by inducing apoptosis of colonic tumor cells through inhibition of HDAC activity. The present study further suggests that changes in intestinal microbiota by SFN, may play a role in chemoprevention against colon cancer.Keywords: sulforaphane, colon cancer, chemoprevention, aberrant crypt foci, intestinal microbiota

scholarly journals Biochemical and molecular aspects of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis: a review

2020 ◽  
Vol 9 (1) ◽  
pp. 2-18 ◽  
Author(s):  
Karthikkumar Venkatachalam ◽  
Ramachandran Vinayagam ◽  
Mariadoss Arokia Vijaya Anand ◽  
Nurulfiza Mat Isa ◽  
Rajasekar Ponnaiyan
Keyword(s):  
Reactive Oxygen Species ◽  
Colon Cancer ◽  
Antioxidant Enzymes ◽  
Alkylating Agent ◽  
Colonic Mucosa ◽  
Colon Carcinogenesis ◽  
Oxygen Species ◽  
Rodent Models ◽  
Metabolic Reactions ◽  
Molecular Aspects

Abstract 1,2-dimethylhydrazine (DMH) is a member in the class of hydrazines, strong DNA alkylating agent, naturally present in cycads. DMH is widely used as a carcinogen to induce colon cancer in animal models. Exploration of DMH-induced colon carcinogenesis in rodent models provides the knowledge to perceive the biochemical, molecular, and histological mechanisms of different stages of colon carcinogenesis. The procarcinogen DMH, after a series of metabolic reactions, finally reaches the colon, there produces the ultimate carcinogen and reactive oxygen species (ROS), which further alkylate the DNA and initiate the development of colon carcinogenesis. The preneolpastic lesions and histopathological observations of DMH-induced colon tumors may provide typical understanding about the disease in rodents and humans. In addition, this review discusses about the action of biotransformation and antioxidant enzymes involved in DMH intoxication. This understanding is essential to accurately identify and interpret alterations that occur in the colonic mucosa when evaluating natural or pharmacological compounds in DMH-induced animal colon carcinogenesis.

scholarly journals Soy Saponins Meditate the Progression of Colon Cancer in Rats by Inhibiting the Activity of β-Glucuronidase and the Number of Aberrant Crypt Foci but Not Cyclooxygenase-2 Activity

ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Yu-Wei Guo ◽  
Yue-Hwa Chen ◽  
Wan-Chun Chiu ◽  
Hsiang Liao ◽  
Shyh-Hsiang Lin
Keyword(s):  
Colon Cancer ◽  
Protein Expression ◽  
Research Methods ◽  
Colonic Mucosa ◽  
Cyclooxygenase 2 ◽  
Aberrant Crypt Foci ◽  
Preneoplastic Lesions ◽  
Pge2 Level ◽  
Cox 2 ◽  
Different Doses

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.

Decreased Histamine Catabolism in the Colonic Mucosa of Patients with Colonic Adenoma

2007 ◽  
Vol 53 (2) ◽  
pp. 436-442 ◽  
Author(s):  
Michael A. Kuefner ◽  
Hubert G. Schwelberger ◽  
Eckhart G. Hahn ◽  
Martin Raithel
Keyword(s):  
Colonic Mucosa ◽  
Colonic Adenoma

scholarly journals Downregulated KIF3B Induced by miR-605-3p Inhibits the Progression of Colon Cancer via Inactivating Wnt/β-Catenin

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Qilong Wang ◽  
Xiaomin Hao ◽  
Gang Xu ◽  
Tiesheng Lv
Keyword(s):  
Colon Cancer ◽  
Tumor Cells ◽  
Malignant Disease ◽  
Luciferase Reporter ◽  
High Morbidity ◽  
Transwell Assay ◽  
Flow Cytometry Assay ◽  
Colon Cells ◽  
Proliferation And Invasion ◽  
Dual Luciferase Reporter Assay

Colon cancer is a common malignant disease with high morbidity and mortality, and miRNA dysfunction has been confirmed as an important reason for cancer development. Several studies have verified miR-605-3p as a tumor inhibitor while its roles in colon cancer remain uncertain. In this study, the specimen of the patients and the cell lines of colon cancer were used to observe the expression of miR-605-3p, and the CCK-8, Transwell assay, and flow cytometry assay were used to observe the functions of miR-605-3p in colon cancer cells. The downstream factors of miR-605-3p were predicted by TargetScan and then were verified by dual-luciferase reporter assay. Moreover, western blot was used to investigate the effect of miR-605-3p on Wnt/β-catenin signal pathway. The result showed that miR-605-3p was extremely downregulated in the pathological tissues and tumor cells, and miR-605-3p could effectively induce the apoptosis and impede the proliferation and invasion of the tumor cells. It was found that KIF3B was a target of KIF3B; decreased KIF3B could reverse the effects of miR-605-3p on colon cancer. Besides, the inactivated Wnt/β-catenin pathway was also observed in colon cells when miR-605-3p was upregulated, and the phenomenon could be rescued by KIF3B upregulation. In conclusion, miR-605-3p could inactivate the Wnt/β-catenin pathway induced via promoting KIF3B expression.

Detection of Lymph Node Micrometastases and Isolated Tumor Cells in Sentinel and Nonsentinel Lymph Nodes of Colon Cancer Patients

2005 ◽  
Vol 29 (9) ◽  
pp. 1172-1175 ◽  
Author(s):  
Andreas Bembenek ◽  
Ulrike Schneider ◽  
Stephan Gretschel ◽  
Joerg Fischer ◽  
Peter M. Schlag
Keyword(s):  
Colon Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Isolated Tumor Cells ◽  
Lymph Node Micrometastases

scholarly journals Iminoflavones Combat 1,2-Dimethyl Hydrazine-Induced Aberrant Crypt Foci Development in Colon Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
V. Ganga Prasad ◽  
Shishir Kawade ◽  
B. S. Jayashree ◽  
Neetinkumar D. Reddy ◽  
Albi Francis ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Treated Group ◽  
Aberrant Crypt Foci ◽  
Colonic Crypts ◽  
Antitumor Potential ◽  
Histopathological Images ◽  
Nuclear Changes ◽  
The Imf

The aim of the present study was to evaluate the antitumor potential of iminoflavones inin vitroandin vivoanticancer models. Preliminary screening in various cancer cell lines revealed four potential iminoflavones out of which IMF-8 was taken based on its activity against colon cancer cells. This was further confirmed by observing the nuclear changes in the cells by AO/EB and Hoechst 33342 staining studies.In vivoactivity was assessed by dimethyl hydrazine-(DMH-) induced colon cancer model in rats. Animals were administered DMH (20 mg/kg, b.w. for 10 weeks and 30 mg/kg b.w.,i.p.for 10 weeks) and were supplemented with (IMF-8) iminoflavone-8 (200 mg/kg,p.o.for 14 days). Results showed that DMH induced 100% aberrant crypt foci (ACF) and polyps which were significantly reduced in the IMF-8 treated group. IMF-8 significantly increased the catalase and GSH levels whereas it reduced the TNF-αand IL-6 levels markedly which suggests the antioxidative and anti-inflammatory actions of flavonoids present in IMF-8. The histopathological images of the IMF-8 treated colon showed no signs of mucosal crypt abscess. These findings suggest that the semi-synthetic iminoflavones, IMF-8, effectively inhibit DMH-induced ACFs and colonic crypts by alleviating the oxidative stress and suppressing the inflammation.

Aberrant Crypt Foci in Colon Cancer Epidemiology

2009 ◽  
pp. 373-386 ◽  
Author(s):  
Sharad Khare ◽  
Kamran Chaudhary ◽  
Marc Bissonnette ◽  
Robert Carroll
Keyword(s):  
Colon Cancer ◽  
Cancer Epidemiology ◽  
Aberrant Crypt Foci

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

2019 ◽  
Vol 149 (2) ◽  
pp. 249-257 ◽  
Author(s):  
Sangyub Kim ◽  
Sabrina P Trudo ◽  
Daniel D Gallaher
Keyword(s):  
Colon Cancer ◽  
Cancer Risk ◽  
Vegetable Consumption ◽  
Aberrant Crypt Foci ◽  
Stem Cell Marker ◽  
Cruciferous Vegetables ◽  
Colon Cancer Risk ◽  
Basal Group ◽  
Marker Expression ◽  
Initiation Stage

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.

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