scholarly journals Anti-Obesity Drug Orlistat Alleviates Western-Diet-Driven Colitis-Associated Colon Cancer via Inhibition of STAT3 and NF-κB-Mediated Signaling

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2060
Author(s):  
Bo-Ram Jin ◽  
Hyo-Jung Kim ◽  
Seo-Ah Sim ◽  
Minho Lee ◽  
Hyo-Jin An
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Survival Rate ◽  
Tumor Progression ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Tumor Formation ◽  
Western Diet ◽  
Cyclin D ◽  
Protein Levels

Many researchers have argued that Western diet (WD)-induced obesity accelerates inflammation and that inflammation is a link between obesity and colorectal cancer (CRC). This study investigated the effect of WDs on the development and progression of colitis-associated colon cancer (CAC) and the efficacy of the anti-obesity agent orlistat on WD-driven CAC in mice. The results revealed that the WD exacerbated CAC in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mice, which showed increased mortality, tumor formation, and aggravation of tumor progression. Furthermore, WD feeding also upregulated inflammation, hyperplasia, and tumorigenicity levels through the activation of STAT3 and NF-κB signaling in an AOM/DSS-induced mouse model. In contrast, treatment with orlistat increased the survival rate and alleviated the symptoms of CAC, including a recovery in colon length and tumor production decreases in WD-driven AOM/DSS-induced mice. Additionally, orlistat inhibited the extent of inflammation, hyperplasia, and tumor progression via the inhibition of STAT3 and NF-κB activation. Treatment with orlistat also suppressed the β-catenin, slug, XIAP, Cdk4, cyclin D, and Bcl-2 protein levels in WD-driven AOM/DSS-induced mice. The results of this study indicate that orlistat alleviates colon cancer promotion in WD-driven CAC mice by suppressing inflammation, especially by inhibiting STAT3 and NF-κB activation.

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 Piperlongumine Alleviates Mouse Colitis and Colitis-Associated Colorectal Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Jia-Rong Huang ◽  
Sheng-Te Wang ◽  
Meng-Ning Wei ◽  
Kun Liu ◽  
Jing-Wen Fu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Epithelial Mesenchymal Transition ◽  
Colonic Neoplasms ◽  
Causative Factor ◽  
Therapeutic Effects ◽  
Acute Colitis ◽  
Related Factors ◽  
Mesenchymal Transition

Colorectal cancer is one of the most common and lethal cancers in the world. An important causative factor of colorectal cancer is ulcerative colitis. In this study, we investigated the therapeutic effects of piperlongumine (PL) on the dextran sulfate sodium (DSS)-induced acute colitis and azoxymethane (AOM)/DSS-induced colorectal cancer mouse models. Our results showed that PL could inhibit the inflammation of DSS-induced mouse colitis and reduce the number of large neoplasms (diameter &gt;2 mm) of AOM/DSS-induced mouse colorectal cancer by downregulation of proinflammatory cytokines cyclooxygenase-2 and interleukin-6 and epithelial-mesenchymal transition-related factors, β-catenin, and snail expressions, but fail to improve the colitis symptoms and to decrease the incidence of colonic neoplasms and the number of small neoplasms (diameter &lt;2 mm). These data suggested that PL might be an effective agent in treating colitis and colorectal cancer.

scholarly journals Dietary Propolis Ameliorates Dextran Sulfate Sodium-Induced Colitis and Modulates the Gut Microbiota in Rats Fed a Western Diet

Nutrients ◽  
2017 ◽  
Vol 9 (8) ◽  
pp. 875 ◽  
Author(s):  
Kai Wang ◽  
Xiaolu Jin ◽  
Mengmeng You ◽  
Wenli Tian ◽  
Richard Leu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Western Diet

scholarly journals The correlation between intestinal microbiota and colorectal cancer

2021 ◽  
Vol 99 (5-6) ◽  
pp. 339-341
Author(s):  
E. M. Lipnitsky ◽  
Yu. S. Medkova ◽  
E. A. Akhmetgalieva ◽  
D. N. Borisova
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Early Diagnosis ◽  
Intestinal Microbiota ◽  
Intestinal Microflora ◽  
Tumor Formation ◽  
Oral Microbiota ◽  
Qualitative Composition ◽  
Oral Microflora ◽  
Identification Of Species

The study of intestinal and oral microflora and their metabolites playing an important role in intestinal homeostasis, has led to the identification of species closely related to the development of colorectal cancer, intracellular correlations of fungi and bacteria compared to control. The correlation between oral microbiota and intestinal microflora, as well as associated with the mucous membrane of the large intestine, was revealed. It was noted that the use of eu- and probiotics improved the immunological indices and the structure of the intestinal microbiota. Thus, studying the oral and intestinal microbiota and its metabolites may prove to be a simple, accessible and informative method for the early diagnosis of colon cancer. However, most studies indicate only changes in the quantitative and qualitative composition of the microbiota, hardly revealing its cause-effect relations with the processes of tumor formation in the colon. Therefore, it is necessary to continue studies of this problem.

Curcumin Inhibits T Follicular Helper Cell Differentiation in Mice with Dextran Sulfate Sodium (DSS)-Induced Colitis

2021 ◽  
pp. 1-19
Author(s):  
Hai-Yan Wang ◽  
Wei Ge ◽  
Su-Qing Liu ◽  
Jian Long ◽  
Qing-Qing Jiang ◽  
...  
Keyword(s):  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Curcuma Longa ◽  
Colon Tissue ◽  
Change Rate ◽  
Protein Levels ◽  
Follicular Helper ◽  
Inflammatory Bowel ◽  
T Follicular Helper Cell ◽  
Pro Inflammatory Cytokines

Follicular helper T cells (Tfh) regulate the differentiation of germinal center B cells and maintain humoral immunity. Notably, imbalances in Tfh differentiation often lead to the development of autoimmune diseases, including inflammatory bowel disease (IBD). Curcumin, a natural product derived from Curcuma longa, is effective in relieving IBD in humans and animals, and its mechanisms of immune regulation need further elaboration. In this study, dextran sodium sulfate induced ulcerative colitis in BALB/c mice, and curcumin was administered simultaneously for 7 days. Curcumin effectively upregulated the change rate of mouse weight, colonic length, down-regulated colonic weight, index of colonic weight, colonic damage score and the levels of pro-inflammatory cytokines IL-6, IL-12, IL-23 and TGF-[Formula: see text]1 in colonic tissues of colitis mice. Importantly, curcumin regulated the differentiation balance of Tfh and their subpopulation in colitis mice; the percentages of Tfh (CD4[Formula: see text]CXCR5[Formula: see text]BCL-6[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]PD-1[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]PD-L1[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]ICOS[Formula: see text], Tfh17 and Tem-Tfh were downregulated significantly, while CD4[Formula: see text]CXCR5[Formula: see text]Blimp-1[Formula: see text], Tfh1, Tfh10, Tfh21, Tfr, Tcm-Tfh and Tem-GC Tfh were upregulated. In addition, curcumin inhibited the expression of Tfh-related transcription factors BCL-6, p-STAT3, Foxp1, Roquin-1, Roquin-2 and SAP, and significantly upregulated the protein levels of Blimp-1 and STAT3 in colon tissue. In conclusion, curcumin may be effective in alleviating dextran sulfate sodium-induced colitis by regulating Tfh differentiation.

scholarly journals NUDT7 Loss Promotes KrasG12D CRC Development

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 576
Author(s):  
Jinsoo Song ◽  
Sujeong Park ◽  
Jinjoo Oh ◽  
Deokha Kim ◽  
Ji Hyun Ryu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lipid Metabolism ◽  
Palmitic Acid ◽  
Wnt Signaling ◽  
Ingenuity Pathway Analysis ◽  
Pathway Analysis ◽  
Lipid Accumulation ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Expression Levels

Studies have suggested that dysregulation of peroxisomal lipid metabolism might play an important role in colorectal cancer (CRC) development. Here, we found that KrasG12D-driven CRC tumors demonstrate dysfunctional peroxisomal β-oxidation and identified Nudt7 (peroxisomal coenzyme A diphosphatase NUDT7) as one of responsible peroxisomal genes. In KrasG12D-driven CRC tumors, the expression level of Nudt7 was significantly decreased. Treatment of azoxymethane/dextran sulfate sodium (AOM/DSS) into Nudt7 knockout (Nudt7−/−) mice significantly induced lipid accumulation and the expression levels of CRC-related genes whereas xenografting of Nudt7-overexpressed LS-174T cells into mice significantly reduced lipid accumulation and the expression levels of CRC-related genes. Ingenuity pathway analysis of microarray using the colon of Nudt7−/− and Nudt7+/+ mice treated with AOM/DSS suggested Wnt signaling as one of activated signaling pathways in Nudt7−/− colons. Upregulated levels of β-catenin were observed in the colons of KrasG12D and AOM/DSS-treated Nudt7−/− mice and downstream targets of β-catenin such as Myc, Ccdn1, and Nos2, were also significantly increased in the colon of Nudt7−/− mice. We observed an increased level of palmitic acid in the colon of Nudt7−/− mice and attachment of palmitic acid-conjugated chitosan patch into the colon of mice induced the expression levels of β-catenin and CRC-related genes. Overall, our data reveal a novel role for peroxisomal NUDT7 in KrasG12D-driven CRC development.

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