scholarly journals Standardized Astragalus Mongholicus Bunge-Curcuma Aromatica Salisb. Extract Efficiently Suppresses Colon Cancer Progression Through Gut Microbiota Modification in CT26-Bearing Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Junfei Gu ◽  
Ruolan Sun ◽  
Qiaohan Wang ◽  
Fuyan Liu ◽  
Decai Tang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Gut Microbiota ◽  
Cancer Progression ◽  
Fatty Acid Content ◽  
Intestinal Barrier ◽  
Mucosal Barrier ◽  
Drug Pair ◽  
Anti Cancer ◽  
Colon Cancer Progression

Altered gut microbiota and a damaged colon mucosal barrier have been implicated in the development of colon cancer. Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (ACE) is a common herbal drug pair that widely used clinically to treat cancer. However, whether the anti-cancer effect of ACE is related to gut microbiota remains unclear yet. We standardized ACE and investigated the effects of ACE on tumour suppression and analyze the related mechanisms on gut microbiota in CT26 colon cancer-bearing mice in the present study. Firstly, four flavonoids (calycosin-7-glucoside, ononin, calycosin, formononetin) and three astragalosides (astragaloside A, astragaloside II, astragaloside I) riched in Astragalus mongholicus Bunge, three curcumins (bisdemethoxycurcumin, demethoxycurcumin, curcumin) and four essential oils (curdione, curzerene, germacrone and β-elemene) from Curcuma aromatica Salisb., in concentrations from 0.08 to 2.07 mg/g, were examined in ACE. Then the results in vivo studies indicated that ACE inhibited solid tumours, liver and spleen metastases of colon cancer while simultaneously reducing pathological tissue damage. Additionally, ACE regulated gut microbiota dysbiosis and the short chain fatty acid content in the gut, repaired intestinal barrier damage. ACE treatment suppressed the overgrowth of conditional pathogenic gut bacteria, including Escherichia-Shigella, Streptococcus and Enterococcus, while the probiotic gut microbiota like Lactobacillus, Roseburia, Prevotellaceae_UCG-001 and Mucispirillum were increased. More interestingly, the content level of SCFAs such as propionic acid and butyric acid was increased after ACE administration, which further mediates intestinal SDF-1/CXCR4 signalling pathway to repair the integrity of the intestinal barrier, decrease Cyclin D1 and C-myc expressions, eventually suppress the tumor the growth and metastasis of colon cancer. To sum up, the present study demonstrated that ACE could efficiently suppress colon cancer progression through gut microbiota modification, which may provide a new explanation of the mechanism of ACE against colon cancer.

Role of MicroRNAs in Colon Cancer Progression and Metastasis

2020 ◽  
Vol 20 ◽  
Author(s):  
Shruthi Sanjitha Sampath ◽  
Sivaramakrishnan Venkatabalsubramanian ◽  
Satish Ramalingam
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Tumour Progression ◽  
Intestinal Barrier ◽  
Colon Cancer Progression ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Novel Therapeutic Strategies

: MicroRNAs regulate gene expression at the posttranscriptional level by binding to the mRNA of their target genes. The dysfunction of miRNAs is strongly associated with the inflammation of the colon. Besides, some microRNAs are shown to suppress tumours while others promote tumour progression and metastasis. Inflammatory bowel diseases include Crohn’s disease and Ulcerative colitis which increase the risk factor for inflammation-associated colon cancer. MicroRNAs are shown to be involved in gastrointestinal pathologies, by targeting the transcripts encoding proteins of the intestinal barrier and their regulators that are associated with inflammation and colon cancer. Detection of these microRNAs in the blood, serum, tissues, faecal matter, etc will enable us to use these microRNAs as biomarkers for early detection of the associated malignancies and design novel therapeutic strategies to overcome the same. Information on MicroRNAs can be applied for the development of targeted therapies against inflammation-mediated colon cancer.

scholarly journals Nobiletin and Derivatives: Functional Compounds from Citrus Fruit Peel for Colon Cancer Chemoprevention

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 867 ◽  
Author(s):  
Goh ◽  
Tan ◽  
Goh ◽  
Chan ◽  
Pusparajah ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Citrus Fruit ◽  
Future Research ◽  
Fruit Peel ◽  
Chemopreventive Agents ◽  
Citrus Peel ◽  
Anti Cancer

The search for effective methods of cancer treatment and prevention has been a continuous effort since the disease was discovered. Recently, there has been increasing interest in exploring plants and fruits for molecules that may have potential as either adjuvants or as chemopreventive agents against cancer. One of the promising compounds under extensive research is nobiletin (NOB), a polymethoxyflavone (PMF) extracted exclusively from citrus peel. Not only does nobiletin itself exhibit anti-cancer properties, but its derivatives are also promising chemopreventive agents; examples of derivatives with anti-cancer activity include 3′-demethylnobiletin (3′-DMN), 4′-demethylnobiletin (4′-DMN), 3′,4′-didemethylnobiletin (3′,4′-DMN) and 5-demethylnobiletin (5-DMN). In vitro studies have demonstrated differential efficacies and mechanisms of NOB and its derivatives in inhibiting and killing of colon cancer cells. The chemopreventive potential of NOB has also been well demonstrated in several in vivo colon carcinogenesis animal models. NOB and its derivatives target multiple pathways in cancer progression and inhibit several of the hallmark features of colorectal cancer (CRC) pathophysiology, including arresting the cell cycle, inhibiting cell proliferation, inducing apoptosis, preventing tumour formation, reducing inflammatory effects and limiting angiogenesis. However, these substances have low oral bioavailability that limits their clinical utility, hence there have been numerous efforts exploring better drug delivery strategies for NOB and these are part of this review. We also reviewed data related to patents involving NOB to illustrate the extensiveness of each research area and its direction of commercialisation. Furthermore, this review also provides suggested directions for future research to advance NOB as the next promising candidate in CRC chemoprevention.

NEAT1 promotes colon cancer progression through sponging miR‐495‐3p and activating CDK6 in vitro and in vivo

2019 ◽  
Vol 234 (11) ◽  
pp. 19582-19591 ◽  
Author(s):  
Zhiyun He ◽  
Jie Dang ◽  
Ailin Song ◽  
Xiang Cui ◽  
Zhijun Ma ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Colon Cancer Progression

scholarly journals Pinocembrin alleviates ulcerative colitis in mice via regulating gut microbiota, suppressing TLR4/MD2/NF-κB pathway and promoting intestinal barrier

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Bei Yue ◽  
Junyu Ren ◽  
Zhilun Yu ◽  
Xiaoping Luo ◽  
Yijing Ren ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Barrier ◽  
Signaling Cascades ◽  
Toll Like Receptor 4 ◽  
Dss Colitis ◽  
Anti Cancer ◽  
Anti Inflammation ◽  
Junction Proteins

Abstract Pinocembrin, a plant-derived flavonoid, has a variety of pharmacological activities, including anti-infection, anti-cancer, anti-inflammation, cardiovascular protection, etc. However, the mechanism of pinocembrin on the anti-colitis efficacy remains elusive and needs further investigation. Here, we reported that pinocembrin eased the severity of dextran sulfate sodium (DSS)-induced colitis in mice by suppressing the abnormal activation of toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signal pathway in vivo. In addition, the gut microbiota was disordered in DSS colitis mice, which was associated with a significant decrease in microbiota diversity and a great shift in bacteria profiles; however, pinocembrin treatment improved the imbalance of gut microbiota and made it similar to that in normal mice. On the other hand, in vitro, pinocembrin down-regulated the TLR4/NF-κB signaling cascades in lipopolysaccharide (LPS)-stimulated macrophages. At the upstream level, pinocembrin competitively inhibited the binding of LPS to myeloid differentiation protein 2 (MD2), thereby blocking the formation of receptor multimer TLR4/MD2·LPS. Furthermore, pinocembrin dose-dependently promoted the expression of tight junction proteins (ZO-1, Claudin-1, Occludin and JAM-A) in Caco-2 cells. In conclusion, our work presented evidence that pinocembrin attenuated DSS-induced colitis in mouse, at least in part, via regulating intestinal microbiota, inhibiting the over-activation of TLR4/MD2/NF-κB signaling pathway, and improving the barriers of intestine.

scholarly journals Overexpression of the transcribed ultraconserved region Uc.138 accelerates colon cancer progression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuki Kuwano ◽  
Kensei Nishida ◽  
Kazuhito Rokutan
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Colon Adenocarcinoma ◽  
Dependent Manner ◽  
Cell Cycle Regulators ◽  
Nuclear Retention ◽  
Exon 2 ◽  
Potential Biomarker ◽  
Colon Cancer Progression

AbstractUltraconserved regions (UCRs) are 481 genomic sequences with 100% identity across humans, rats, and mice. Increasing evidence suggests that non-coding RNAs transcribed from UCRs are involved in various diseases, especially cancers. The human transformer 2β gene (TRA2B) encodes a UCR (uc.138) that spans exon 2 and its neighboring introns. TRA2B4 RNA is the only transcript that contains the whole exon 2 among five spliced TRA2B RNA variants (TRA2B1-5). TRA2B4 is upregulated in colon cancer cell lines, although it is not translated to Tra2β protein because of its nuclear retention. Nevertheless, the clinical significance and biological functions of uc.138 in colon cancer cells remain unclear. In this study, RNA in situ hybridization showed that TRA2B4 was predominantly overexpressed in the nucleus of colon adenocarcinoma and adenoma. Overexpression of TRA2B4 in colon cancer HCT116 cells promoted cell proliferation by changing the expression of G2/M-related cell cycle regulators. Moreover, TRA2B4 increased migration and cell viability in a uc.138 sequence-dependent manner. TRA2B4 significantly enhanced tumorigenesis in vivo. Taken together, uc.138 encoded in TRA2B4 plays an oncogenic role in tumor progression and may become a potential biomarker and therapeutic target in colon cancer.

scholarly journals SGLT2 inhibition slows tumor growth in mice by reversing hyperinsulinemia

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Ali R. Nasiri ◽  
Marcos R. Rodrigues ◽  
Zongyu Li ◽  
Brooks P. Leitner ◽  
Rachel J. Perry
Keyword(s):  
Colon Cancer ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Colon Adenocarcinoma ◽  
Sglt2 Inhibitors ◽  
Multiple Tumor ◽  
Increased Risk ◽  
Colon Cancer Progression

Abstract Background Obesity confers an increased risk and accelerates the progression of multiple tumor types in rodents and humans, including both breast and colon cancer. Because sustained weight loss is rarely achieved, therapeutic approaches to slow or prevent obesity-associated cancer development have been limited, and mechanistic insights as to the obesity-cancer connection have been lacking. Methods E0771 breast tumors and MC38 colon tumors were treated in vivo in mice and in vitro with two mechanistically different insulin-lowering agents, a controlled-release mitochondrial protonophore (CRMP) and sodium-glucose cotransporter-2 (SGLT2) inhibitors, and tumor growth and glucose metabolism were assessed. Groups were compared by ANOVA with Bonferroni’s multiple comparisons test. Results Dapagliflozin slows tumor growth in two mouse models (E0771 breast cancer and MC38 colon adenocarcinoma) of obesity-associated cancers in vivo, and a mechanistically different insulin-lowering agent, CRMP, also slowed breast tumor growth through its effect to reverse hyperinsulinemia. In both models and with both agents, tumor glucose uptake and oxidation were not constitutively high, but were hormone-responsive. Restoration of hyperinsulinemia by subcutaneous insulin infusion abrogated the effects of both dapagliflozin and CRMP to slow tumor growth. Conclusions Taken together, these data demonstrate that hyperinsulinemia per se promotes both breast and colon cancer progression in obese mice, and highlight SGLT2 inhibitors as a clinically available means of slowing obesity-associated tumor growth due to their glucose- and insulin-lowering effects.

scholarly journals The cables gene on chromosome 18Q regulates colon cancer progression in vivo

2005 ◽  
Vol 4 (8) ◽  
pp. 861-863 ◽  
Author(s):  
Sandra D. Kirley ◽  
Massimo D'Apuzzo ◽  
Gregory Y. Lauwers ◽  
Fiona Graeme-Cook ◽  
Daniel C. Chung ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Colon Cancer Progression ◽  
Chromosome 18Q

scholarly journals Therapeutic targeting of SLC6A8 creatine transporter inhibits KRAS mutant and wildtype colon cancer and modulates human creatine levels

2021 ◽  
Author(s):  
Isabel Kurth ◽  
Norihiro Yamaguchi ◽  
Celia Andreu-Agullo ◽  
Helen S. Tian ◽  
Subhasree Sridhar ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Phase 1 ◽  
Creatine Transporter ◽  
Tumor Cell Apoptosis ◽  
Creatine Kinase B ◽  
Colon Cancer Progression ◽  
Creatine Metabolism

ABSTRACTColorectal cancer (CRC) is a leading cause of cancer mortality. Creatine metabolism was previously shown to critically regulate colon cancer progression. We report that RGX-202, an oral small-molecule SLC6A8 creatine transporter inhibitor, robustly inhibits creatine import in vitro and in vivo, reduces intracellular phosphocreatine and ATP levels and induces tumor cell apoptosis in CRC. RGX-202 suppressed tumor growth across KRAS wild-type and KRAS mutant xenograft, syngeneic and patient-derived xenograft colorectal cancers. Anti-tumor efficacy correlated with tumoral expression of creatine kinase B. Combining RGX-202 with 5- fluorouracil or the DHODH inhibitor leflunomide caused regressions of multiple colorectal xenograft and PDX tumors of distinct mutational backgrounds. RGX-202 also perturbed creatine metabolism in metastatic CRC patients enrolled in a Phase-1 trial, mirroring pharmacodynamic effects on creatine metabolism observed in mice. This is, to our knowledge, the first demonstration of pre-clinical and human pharmacodynamic activity for creatine metabolism targeting in oncology, revealing a critical target for CRC.

scholarly journals Lnc HAGLR Promotes Colon Cancer Progression Through Sponging miR‐185‐5p and Activating CDK4 and CDK6 in vitro and in vivo

2020 ◽  
Vol Volume 13 ◽  
pp. 5913-5925 ◽  
Author(s):  
Weixuan Sun ◽  
Wenting Nie ◽  
Zhaoyi Wang ◽  
Haolong Zhang ◽  
Yezhou Li ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Colon Cancer Progression

scholarly journals Knockdown of Lymphoid Enhancer factor 1 Inhibits Colon Cancer Progression In Vitro and In Vivo

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e76596 ◽  
Author(s):  
Wen-Juan Wang ◽  
Yu Yao ◽  
Li-Li Jiang ◽  
Ting-Hua Hu ◽  
Jie-Qun Ma ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Colon Cancer Progression ◽  
Enhancer Factor
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