scholarly journals Dietary Barley Leaf Mitigates Tumorigenesis in Experimental Colitis-Associated Colorectal Cancer

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3487
Author(s):  
Daotong Li ◽  
Yu Feng ◽  
Meiling Tian ◽  
Xiaosong Hu ◽  
Ruimao Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Experimental Colitis ◽  
Tumor Formation ◽  
Colorectal Carcinogenesis ◽  
Mucosal Barrier ◽  
Hordeum Vulgare L ◽  
Proliferation Markers ◽  
Potential Health ◽  
Expression Of Genes ◽  
Colorectal Cancer Prevention

Dietary barley (Hordeum vulgare L.) leaf (BL) is a popular functional food known to have potential health benefits; however, the effect of BL in colorectal cancer prevention has not been examined. Here, we examined the role of BL on the prevention of colorectal carcinogenesis and defined the mechanism involved. BL supplementation could protect against weight loss, mitigate tumor formation, and diminish histologic damage in mice treated with azoxymethane (AOM) and dextran sulfate sodium (DSS). Moreover, BL suppressed colonic expression of inflammatory enzymes, while improving the mucosal barrier dysfunctions. The elevated levels of cell proliferation markers and the increased expression of genes involved in β-catenin signaling were also reduced by BL. In addition, analyses of microbiota revealed that BL prevented AOM/DSS-induced gut microbiota dysbiosis by promoting the enrichment of Bifidobacterium. Overall, these data suggest that BL is a promising dietary agent for preventing colitis-associated colorectal cancer.

scholarly journals Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC

2017 ◽  
Vol 114 (37) ◽  
pp. E7697-E7706 ◽  
Author(s):  
Kiyotoshi Satoh ◽  
Shinichi Yachida ◽  
Masahiro Sugimoto ◽  
Minoru Oshima ◽  
Toshitaka Nakagawa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Gene Mutations ◽  
Metabolic Reprogramming ◽  
Colorectal Carcinogenesis ◽  
Specific Gene ◽  
Control Mechanisms ◽  
Pyrimidine Synthesis ◽  
Expression Of Genes

Cancer cells alter their metabolism for the production of precursors of macromolecules. However, the control mechanisms underlying this reprogramming are poorly understood. Here we show that metabolic reprogramming of colorectal cancer is caused chiefly by aberrant MYC expression. Multiomics-based analyses of paired normal and tumor tissues from 275 patients with colorectal cancer revealed that metabolic alterations occur at the adenoma stage of carcinogenesis, in a manner not associated with specific gene mutations involved in colorectal carcinogenesis. MYC expression induced at least 215 metabolic reactions by changing the expression levels of 121 metabolic genes and 39 transporter genes. Further, MYC negatively regulated the expression of genes involved in mitochondrial biogenesis and maintenance but positively regulated genes involved in DNA and histone methylation. Knockdown of MYC in colorectal cancer cells reset the altered metabolism and suppressed cell growth. Moreover, inhibition of MYC target pyrimidine synthesis genes such as CAD, UMPS, and CTPS blocked cell growth, and thus are potential targets for colorectal cancer therapy.

scholarly journals Dietary Supplementation of Selenoneine-Containing Tuna Dark Muscle Extract Effectively Reduces Pathology of Experimental Colorectal Cancers in Mice

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1380 ◽  
Author(s):  
Junko Masuda ◽  
Chiho Umemura ◽  
Miki Yokozawa ◽  
Ken Yamauchi ◽  
Takuya Seko ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Antioxidant Activities ◽  
Cancer Cell Line ◽  
Suppressor Cells ◽  
Interferon Γ ◽  
Tumor Formation ◽  
Colorectal Carcinogenesis ◽  
Colorectal Cancer Cell Line ◽  
Dark Muscle ◽  
Muscle Extract

Selenoneine is an ergothioneine analog with greater antioxidant activity and is the major form of organic selenium in the blood, muscles, and other tissues of tuna. The aim of this study was to determine whether a selenoneine-rich diet exerts antioxidant activities that can prevent carcinogenesis in two types of colorectal cancer model in mice. We administrated selenoneine-containing tuna dark muscle extract (STDME) to mice for one week and used azoxymethane (AOM) and dextran sodium sulfate (DSS) for inducing colorectal carcinogenesis. Next, we examined the incidence of macroscopic polyps and performed functional analysis of immune cells from the spleen. We also studied tumor formation rates and median survival following the subcutaneous implantation of a colorectal cancer cell line. In the AOM/DSS-induced colitis-associated cancer (CAC) model, the oral administration of STDME significantly decreased tumor incidence and inhibited the accumulation of myeloid-derived suppressor cells (MDSCs) while also inhibiting the downregulation of interferon-γ (IFN-γ) production during carcinogenesis. These results suggest that dietary STDME may be an effective agent for reducing colorectal tumor progression.

scholarly journals The Role of Gut Barrier Dysfunction and Microbiome Dysbiosis in Colorectal Cancer Development

2021 ◽  
Vol 11 ◽  
Author(s):  
Flavia Genua ◽  
Vedhika Raghunathan ◽  
Mazda Jenab ◽  
William M. Gallagher ◽  
David J. Hughes
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Gut Microbiome ◽  
Colorectal Carcinogenesis ◽  
Mucosal Barrier ◽  
Colonic Epithelium ◽  
Barrier Dysfunction ◽  
Gut Barrier ◽  
Mucosal Barrier Function ◽  
And Oxidative Stress

Accumulating evidence indicates that breakdown of the+ protective mucosal barrier of the gut plays a role in colorectal cancer (CRC) development. Inflammation and oxidative stress in the colonic epithelium are thought to be involved in colorectal carcinogenesis and the breakdown of the integrity of the colonic barrier may increase the exposure of colonocytes to toxins from the colonic milieu, enhancing inflammatory processes and release of Reactive Oxygen Species (ROS). The aetiological importance of the gut microbiome and its composition – influenced by consumption of processed meats, red meats and alcoholic drinks, smoking, physical inactivity, obesity - in CRC development is also increasingly being recognized. The gut microbiome has diverse roles, such as in nutrient metabolism and immune modulation. However, microbial encroachment towards the colonic epithelium may promote inflammation and oxidative stress and even translocation of species across the colonic lumen. Recent research suggests that factors that modify the above mechanisms, e.g., obesity and Western diet, also alter gut microbiota, degrade the integrity of the gut protective barrier, and expose colonocytes to toxins. However, it remains unclear how obesity, lifestyle and metabolic factors contribute to gut-barrier integrity, leading to metabolic disturbance, colonocyte damage, and potentially to CRC development. This review will discuss the interactive roles of gut-barrier dysfunction, microbiome dysbiosis, and exposure to endogenous toxins as another mechanism in CRC development, and how biomarkers of colonic mucosal barrier function may provide avenues for disease, prevention and detection.

scholarly journals Cardamonin Attenuates Experimental Colitis and Associated Colorectal Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 661
Author(s):  
Shirley James ◽  
Jayasekharan S. Aparna ◽  
Anu Babu ◽  
Aswathy Mary Paul ◽  
Manendra Babu Lankadasari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Experimental Colitis ◽  
Tumor Formation ◽  
Raw 264.7 Cells ◽  
Wide Range ◽  
Nitrous Oxide Production ◽  
Anti Inflammatory

Cardamonin is a naturally occurring chalcone, majorly from the Zingiberaceae family, which includes a wide range of spices from India. Herein, we investigated the anti-inflammatory property of cardamonin using different in vitro and in vivo systems. In RAW 264.7 cells, treatment with cardamonin showed a reduced nitrous oxide production without affecting the cell viability and decreased the expression of iNOS, TNF-α, and IL-6, and inhibited NF-kB signaling which emphasizes the role of cardamonin as an anti-inflammatory molecule. In a mouse model of dextran sodium sulfate (DSS)-induced colitis, cardamonin treatment protected the mice from colitis. Subsequently, we evaluated the therapeutic potential of this chalcone in a colitis-associated colon cancer model. We performed microRNA profiling in the different groups and observed that cardamonin modulates miRNA expression, thereby inhibiting tumor formation. Together, our findings indicate that cardamonin has the potential to be considered for future therapy against colorectal cancer.

Fiber-associated wheat lignans and colorectal cancer prevention

2021 ◽  
pp. 115-136
Author(s):  
Jingwen Xu ◽  
◽  
Weiqun Wang ◽  
◽  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Prevention ◽  
Clinical Intervention ◽  
Epidemiological Studies ◽  
Study Data ◽  
Potential Health ◽  
Cycle Arrest ◽  
Animal Data ◽  
Anti Oxidant ◽  
Colorectal Cancer Prevention

Wheat, as a staple food, has been largely consumed worldwide. In addition to nutritional values, whole grain including fiber-enriched wheat bran has been reported to provide many nutraceuticals such as wheat lignans. This chapter reviews recent epidemiological and animal data on wheat lignans and their role in colorectal cancer prevention. It covers aspects of the lignan structure, biosynthesis, analysis, metabolism and potential health benefits with emphasis on anti-proliferative, anti-oxidant, anti-inflammation, anti-estrogenic and cell cycle arrest mechanisms. Human epidemiological studies suggest dietary intake of lignans is associated with reducing risk of many chronic diseases such as cardiovascular disease, chronic bowel inflammation, and certain types of cancer including colorectal cancer. The bioactivity of wheat lignans has been shown to be influenced by their chemical forms and microbial flora-induced metabolites. Compelling animal study data suggest that dietary lignans or wheat lignans contribute to colorectal cancer prevention; however, further clinical intervention studies appear warranted.

A Tale of Two Colons and Two Cancers

Swiss Surgery ◽  
2003 ◽  
Vol 9 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Gervaz ◽  
Bühler ◽  
Scheiwiller ◽  
Morel
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Splenic Flexure ◽  
Chromosomal Instability ◽  
Proximal Colon ◽  
Colorectal Carcinogenesis ◽  
Physiological Data ◽  
Central Hypothesis ◽  
Group Stratification

The central hypothesis explored in this paper is that colorectal cancer (CRC) is a heterogeneous disease. The initial clue to this heterogeneity was provided by genetic findings; however, embryological and physiological data had previously been gathered, showing that proximal (in relation to the splenic flexure) and distal parts of the colon represent distinct entities. Molecular biologists have identified two distinct pathways, microsatellite instability (MSI) and chromosomal instability (CIN), which are involved in CRC progression. In summary, there may be not one, but two colons and two types of colorectal carcinogenesis, with distinct clinical outcome. The implications for the clinicians are two-folds; 1) tumors originating from the proximal colon have a better prognosis due to a high percentage of MSI-positive lesions; and 2) location of the neoplasm in reference to the splenic flexure should be documented before group stratification in future trials of adjuvant chemotherapy in patients with stage II and III colon cancer.

Regulation of microRNAs in Inflammation-Associated Colorectal Cancer: A Mechanistic Approach

2020 ◽  
Vol 20 ◽  
Author(s):  
Sridhar Muthusami ◽  
Ilangovan Ramachandran ◽  
Sneha Krishnamoorthy ◽  
Yuvaraj Sambandam ◽  
Satish Ramalingam ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Colorectal Carcinogenesis ◽  
Model Systems ◽  
Necrosis Factor Alpha ◽  
Multi Stage ◽  
Mechanistic Approach ◽  
Tnf Α ◽  
Factor Alpha

: The development of colorectal cancer (CRC) is a multi-stage process. The inflammation of the colon as in inflammatory bowel disease (IBD) such as ulcerative colitis (UC) or Crohn’s disease (CD) is often regarded as the initial trigger for the development of CRC. Many cytokines such as tumor necrosis factor alpha (TNF-α) and several interleukins (ILs) are known to exert proinflammatory actions, and inflammation initiates or promotes tumorigenesis of various cancers, including CRC through differential regulation of microRNAs (miRNAs/miRs). miRNAs can be oncogenic miRNAs (oncomiRs) or anti-oncomiRs/tumor suppressor miRNAs, and they play key roles during colorectal carcinogenesis. However, the functions and molecular mechanisms of regulation of miRNAs involved in inflammation-associated CRC are still anecdotal and largely unknown. Consolidating the published results and offering perspective solutions to circumvent CRC, the current review is focused on the role of miRNAs and their regulation in the development of CRC. We have also discussed the model systems adapted by researchers to delineate the role of miRNAs in inflammation-associated CRC.

A Dinucleotide Deletion in the CD24 Gene Is a Potential Risk Factor for Colorectal Cancer

2020 ◽  
Vol 86 (5) ◽  
pp. 480-485
Author(s):  
Lior Segev ◽  
Ilana Naboishchikov ◽  
Diana Kazanov ◽  
Ezra Bernstein ◽  
Meital Shaked ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Peripheral Blood ◽  
Intracellular Signaling ◽  
Genetic Variant ◽  
Colorectal Carcinogenesis ◽  
Polymorphism Analysis ◽  
Peripheral Blood Leukocytes ◽  
Clinical Value ◽  
Blood Leukocytes ◽  
Multistep Process

Background CD24 is a sialoglycoprotein anchored to the cell surface via glycosylphosphatidylinositol and is involved in intracellular signaling processes. It plays an important role in the early stages of the multistep process of colorectal carcinogenesis. Several single nucleotide polymorphisms in the CD24 gene are reported to exert a diverse effect on cancer risk. We aimed to elucidate whether CD24 TG/del genetic variants are associated with susceptibility to colorectal cancer (CRC). Methods The study included 179 subjects, 36 with CRC (prior to surgery) and 143 healthy control subjects. Deoxyribonucleic acid was purified from peripheral blood leukocytes, and by using restriction fragment length polymorphism analysis, the CD24 gene was genotyped for the specific genetic variant, TG deletion. Additionally, CD24 protein expression levels were determined by Western blotting analysis. Results The incidence of the TG/del was higher among the CRC patients compared with healthy controls, 14% and 10%, respectively ( P = .54). CD24 protein levels were significantly higher among CRC patients. There were no significant differences in CD24 expression between CRC patients at different stages of the disease or between patients who carry the mutation and those who did not. Conclusions CD24 genetic variant might be of clinical value for risk assessment as part of cancer prevention programs. Further study on larger populations is needed to validate the importance of this dinucleotide deletion in CRC development. Overexpression of CD24 protein occurs early along the multistep process of CRC carcinogenesis, and a simple blood sample based on CD24 expression on peripheral blood leukocytes can contribute to early diagnosis.

scholarly journals Circulating let-7e-5p, miR-106a-5p, miR-28-3p, and miR-542-5p as a Promising microRNA Signature for the Detection of Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1493
Author(s):  
Camila Meirelles S. Silva ◽  
Mateus C. Barros-Filho ◽  
Deysi Viviana T. Wong ◽  
Julia Bette H. Mello ◽  
Livia Maria S. Nobre ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Unmet Need ◽  
Area Under The Curve ◽  
Discrimination Performance ◽  
Colorectal Carcinogenesis ◽  
The Cancer Genome Atlas ◽  
Colon Perforation ◽  
Data Series ◽  
Predictive Tool ◽  
Incidence And Mortality

Colorectal cancer (CRC) is a disease with high incidence and mortality. Colonoscopy is a gold standard among tests used for CRC traceability. However, serious complications, such as colon perforation, may occur. Non-invasive diagnostic procedures are an unmet need. We aimed to identify a plasma microRNA (miRNA) signature for CRC detection. Plasma samples were obtained from subjects (n = 109) at different stages of colorectal carcinogenesis. The patients were stratified into a non-cancer (27 healthy volunteers, 17 patients with hyperplastic polyps, 24 with adenomas), and a cancer group (20 CRC and 21 metastatic CRC). miRNAs (381) were screened by TaqMan Low-Density Array. A classifier based on four differentially expressed miRNAs (miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p) was able to discriminate cancer versus non-cancer cases. The overexpression of these miRNAs was confirmed by RT-qPCR, and a cross-study validation step was implemented using eight data series retrieved from Gene Expression Omnibus (GEO). In addition, another external data validation using CRC surgical specimens from The Cancer Genome Atlas (TCGA) was carried out. The predictive model’s performance in the validation set was 76.5% accuracy, 59.4% sensitivity, and 86.8% specificity (area under the curve, AUC = 0.716). The employment of our model in the independent publicly available datasets confirmed a good discrimination performance in five of eight datasets (median AUC = 0.823). Applying this algorithm to the TCGA cohort, we found 99.5% accuracy, 99.7% sensitivity, and 90.9% specificity (AUC = 0.998) when the model was applied to solid colorectal tissues. Overall, we suggest a novel signature of four circulating miRNAs, i.e., miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p, as a predictive tool for the detection of CRC.

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