The role of butyrate in surgical and oncological outcomes in colorectal cancer

2021 ◽  
Author(s):  
Roy Hajjar ◽  
Carole S Richard ◽  
Manuela M Santos
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Current Knowledge ◽  
Intestinal Barrier ◽  
Inhibitory Effect ◽  
Intestinal Barrier Function ◽  
Current Evidence ◽  
Mucus Production ◽  
Antineoplastic Effect ◽  
The Impact

Butyrate is a short-chain fatty acid produced by colonic gut bacteria as a result of fermentation of dietary fibers. In the colon, butyrate is a major energy substrate and contributes to the nutritional support and proliferation of a healthy mucosa. It also promotes the intestinal barrier function by enhancing mucus production and tight junctions. In addition to its pro-proliferative effect in healthy colonocytes, butyrate inhibits the proliferation of cancer cells. The antineoplastic effect of butyrate is associated with the inhibitory effect of butyrate on histone deacetylase (HDAC) enzymes, which promote carcinogenesis. Due to the metabolic shift of cancer cells toward glycolysis, unused butyrate accumulates and inhibits procarcinogenic HDACs. In addition, recent studies suggest that butyrate may improve the healing of colonic tissue after surgery in animal models, specifically at the site of reconnection of colonic ends - anastomosis - after surgical resection. Here, we review current evidence on the impact of butyrate on epithelial integrity and colorectal cancer and present current knowledge on data that support its potential applications in surgical practice.

scholarly journals Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3

2021 ◽  
Vol 22 (15) ◽  
pp. 8117
Author(s):  
Nunzia D’Onofrio ◽  
Elisa Martino ◽  
Luigi Mele ◽  
Antonino Colloca ◽  
Martina Maione ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Current Knowledge ◽  
Apoptotic Cell ◽  
Critical Role ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Protein Levels

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.

scholarly journals Probiotics: A Promising Candidate for Management of Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3178
Author(s):  
Ashutosh Tripathy ◽  
Jayalaxmi Dash ◽  
Sudhakar Kancharla ◽  
Prachetha Kolli ◽  
Deviyani Mahajan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Treatment Strategies ◽  
Intestinal Barrier ◽  
World Health ◽  
Intestinal Barrier Function ◽  
Cancer Type ◽  
Prevention Therapy ◽  
Long Time ◽  
Health Organization ◽  
Cancerous Cells

Colorectal cancer (CRC) is the World’s third most frequently diagnosed cancer type. It accounted for about 9.4% mortality out of the total incidences of cancer in the year 2020. According to estimated facts by World Health Organization (WHO), by 2030, 27 million new CRC cases, 17 million deaths, and around 75 million people living with the disease will appear. The facts and evidence that establish a link between the intestinal microflora and the occurrence of CRC are quite intuitive. Current shortcomings of chemo- and radiotherapies and the unavailability of appropriate treatment strategies for CRC are becoming the driving force to search for an alternative approach for the prevention, therapy, and management of CRC. Probiotics have been used for a long time due to their beneficial health effects, and now, it has become a popular candidate for the preventive and therapeutic treatment of CRC. The probiotics adopt different strategies such as the improvement of the intestinal barrier function, balancing of natural gut microflora, secretion of anticancer compounds, and degradation of carcinogenic compounds, which are useful in the prophylactic treatment of CRC. The pro-apoptotic ability of probiotics against cancerous cells makes them a potential therapeutic candidate against cancer diseases. Moreover, the immunomodulatory properties of probiotics have created interest among researchers to explore the therapeutic strategy by activating the immune system against cancerous cells. The present review discusses in detail different strategies and mechanisms of probiotics towards the prevention and treatment of CRC.

scholarly journals Emc3 maintains intestinal homeostasis by preserving secretory lineages

2021 ◽  
Author(s):  
Meina Huang ◽  
Li Yang ◽  
Ning Jiang ◽  
Quanhui Dai ◽  
Runsheng Li ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Dominant Role ◽  
Paneth Cell ◽  
Intestinal Barrier ◽  
Goblet Cells ◽  
Paneth Cells ◽  
Intestinal Barrier Function ◽  
Endoplasmic Reticulum Membrane ◽  
Mucus Production

AbstractIntestinal exocrine secretory lineages, including goblet cells and Paneth cells, provide vital innate host defense to pathogens. However, how these cells are specified and maintained to ensure intestinal barrier function remains poorly defined. Here we show that endoplasmic reticulum membrane protein complex subunit 3 (Emc3) is essential for differentiation and function of exocrine secretory lineages. Deletion of Emc3 in intestinal epithelium decreases mucus production by goblet cells and Paneth cell population, along with gut microbial dysbiosis, which result in spontaneous inflammation and increased susceptibility to DSS-induced colitis. Moreover, Emc3 deletion impairs stem cell niche function of Paneth cells, thus resulting in intestinal organoid culture failure. Mechanistically, Emc3 deficiency leads to increased endoplasmic reticulum (ER) stress. Mitigating ER stress with tauroursodeoxycholate acid alleviates secretory dysfunction and restores organoid formation. Our study identifies a dominant role of Emc3 in maintaining intestinal mucosal homeostasis.

scholarly journals MicroRNA-124 Regulates the Proliferation of Colorectal Cancer Cells by TargetingiASPP

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Kuijie Liu ◽  
Hua Zhao ◽  
Hongliang Yao ◽  
Sanlin Lei ◽  
Zhendong Lei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Target Prediction ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Small Noncoding Rnas ◽  
Colorectal Cancer Cells ◽  
Microrna 124

MicroRNAs are a class of small, noncoding RNAs that function as critical regulators of gene expression by targeting mRNAs for translational repression or degradation. In this study, we demonstrate that expression of microRNA-124 (miR-124) is significantly downregulated in colorectal cancer tissues and cell lines, compared to the matched adjacent tissues. We identified and confirmed inhibitor of apoptosis-stimulating protein of p53 (iASPP) as a novel, direct target of miR-124 using target prediction algorithms and luciferase reporter gene assays. Overexpression of miR-124 suppressed iASPP protein expression, upregulated expression of the downstream signaling molecule nuclear factor-kappa B (NF-κB), and attenuated cell viability, proliferation, and colony formation in SW480 and HT-29 colorectal cancer cells in vitro. Forced overexpression ofiASPPpartly rescued the inhibitory effect of miR-124 on SW480 and HT29 cell proliferation. Taken together, these findings shed light on the role and mechanism of action of miR-124, indicate that the miR-124/iASPP axis can regulate the proliferation of colorectal cancer cells, and suggest that miR-124 may serve as a potential therapeutic target for colorectal cancer.

scholarly journals Current knowledge on non-steroidal anti-inflammatory drug-induced small-bowel damage: a comprehensive review

2019 ◽  
Vol 55 (5) ◽  
pp. 481-495 ◽  
Author(s):  
Toshio Watanabe ◽  
Yasuhiro Fujiwara ◽  
Francis K. L. Chan
Keyword(s):  
Small Bowel ◽  
Current Knowledge ◽  
Significant Proportion ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Drug Induced ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Small Bowel Endoscopy ◽  
Intestinal Ulcers

AbstractRecent advances in small-bowel endoscopy such as capsule endoscopy have shown that non-steroidal anti-inflammatory drugs (NSAIDs) frequently damage the small intestine, with the prevalence rate of mucosal breaks of around 50% in chronic users. A significant proportion of patients with NSAIDs-induced enteropathy are asymptomatic, but some patients develop symptomatic or complicated ulcers that need therapeutic intervention. Both inhibition of prostaglandins due to the inhibition of cyclooxygenases and mitochondrial dysfunction secondary to the topical effect of NSAIDs play a crucial role in the early process of injury. As a result, the intestinal barrier function is impaired, which allows enterobacteria to invade the mucosa. Gram-negative bacteria and endogenous molecules coordinate to trigger inflammatory cascades via Toll-like receptor 4 to induce excessive expression of cytokines such as tumor necrosis factor-α and to activate NLRP3 inflammasome, a multiprotein complex that processes pro-interleukin-1β into its mature form. Finally, neutrophils accumulate in the mucosa, resulting in intestinal ulceration. Currently, misoprostol is the only drug that has a proven beneficial effect on bleeding small intestinal ulcers induced by NSAIDs or low-dose aspirin, but its protection is insufficient. Therefore, the efficacy of the combination of misoprostol with other drugs, especially those targeting the innate immune system, should be assessed in the next step.

scholarly journals Dietary Betaine Improves Intestinal Barrier Function and Ameliorates the Impact of Heat Stress in Multiple Vital Organs as Measured by Evans Blue Dye in Broiler Chickens

Animals ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 38 ◽  
Author(s):  
Majid Shakeri ◽  
Jeremy James Cottrell ◽  
Stuart Wilkinson ◽  
Weicheng Zhao ◽  
Hieu Huu Le ◽  
...  
Keyword(s):  
Heat Stress ◽  
Evans Blue ◽  
Broiler Chickens ◽  
Control Diet ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Blue Dye ◽  
Evans Blue Dye ◽  
Villous Height ◽  
The Impact

In a 2 × 2 factorial design, 60 male Ross-308 broilers were fed either a control or 1 g/kg betaine diet and housed under thermoneutral (TN) or heat stress (HS) conditions. Broilers were acclimated to diets for 1 week under TN (25 °C), then either kept at TN or HS, where the temperature increased 8 h/day at 33 °C and 16 h/day at 25 °C for up to 10 days. Respiration rate (RR) was measured at four time points, and on each of 1, 2, 3, 7 and 10 days of HS, 12 broilers were injected with 0.5 mg/kg of Evans Blue Dye (EBD) solution to quantify regional changes in tissue damage. Betaine was quantified in tissues, and ileal damage was assessed via morphometry and transepithelial resistance (TER). Heat stress elevated RR (p < 0.001) and resulted in reduced villous height (p = 0.009) and TER (p < 0.001), while dietary betaine lowered RR during HS (p < 0.001), increased betaine distribution into tissues, and improved ileal villous height (p < 0.001) and TER (p = 0.006). Heat stress increased EBD in the muscle and kidney of chickens fed the control diet but not in those receiving betaine. Overall, these data indicate that supplemented betaine is distributed to vital organs and the gastrointestinal tract, where it is associated with improved tolerance of HS. Furthermore, EBD markers help reveal the effects of HS on organs dysfunction.

scholarly journals The Intestinal Fate of Citrus Flavanones and Their Effects on Gastrointestinal Health

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1464 ◽  
Author(s):  
Yala Stevens ◽  
Evelien Van Rymenant ◽  
Charlotte Grootaert ◽  
John Van Camp ◽  
Sam Possemiers ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
Human Subjects ◽  
Intestinal Barrier ◽  
Intestinal Bacteria ◽  
Intestinal Microbiome ◽  
Intestinal Barrier Function ◽  
Current Evidence ◽  
Gastrointestinal Health ◽  
Beneficial Effects

Citrus flavanones, with hesperidin and naringin as the most abundant representatives, have various beneficial effects, including anti-oxidative and anti-inflammatory activities. Evidence also indicates that they may impact the intestinal microbiome and are metabolized by the microbiota as well, thereby affecting their bioavailability. In this review, we provide an overview on the current evidence on the intestinal fate of hesperidin and naringin, their interaction with the gut microbiota, and their effects on intestinal barrier function and intestinal inflammation. These topics will be discussed as they may contribute to gastrointestinal health in various diseases. Evidence shows that hesperidin and naringin are metabolized by intestinal bacteria, mainly in the (proximal) colon, resulting in the formation of their aglycones hesperetin and naringenin and various smaller phenolics. Studies have also shown that citrus flavanones and their metabolites are able to influence the microbiota composition and activity and exert beneficial effects on intestinal barrier function and gastrointestinal inflammation. Although the exact underlying mechanisms of action are not completely clear and more research in human subjects is needed, evidence so far suggests that citrus flavanones as well as their metabolites have the potential to contribute to improved gastrointestinal function and health.

scholarly journals Novel proapoptotic agent SM-1 enhances the inhibitory effect of 5-fluorouracil on colorectal cancer cells in vitro and in vivo

2017 ◽  
Vol 13 (6) ◽  
pp. 4762-4768 ◽  
Author(s):  
Ying Wang ◽  
Shoujun Yuan ◽  
Linna Li ◽  
Dexuan Yang ◽  
Chengwang Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Colorectal Cancer Cells

scholarly journals Inhibitory effect of maple syrup on the cell growth and invasion of human colorectal cancer cells

2015 ◽  
Vol 33 (4) ◽  
pp. 1579-1584 ◽  
Author(s):  
TETSUSHI YAMAMOTO ◽  
KENTARO UEMURA ◽  
KAHO MORIYAMA ◽  
KUNIKO MITAMURA ◽  
ATSUSHI TAGA
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Human Colorectal Cancer ◽  
Maple Syrup ◽  
Colorectal Cancer Cells ◽  
Human Colorectal Cancer Cells
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