scholarly journals Chemoprevention of Colon and Small Intestinal Tumorigenesis in APCMin/+ Mice by Licofelone, a Novel Dual 5-LOX/COX Inhibitor: Potential Implications for Human Colon Cancer Prevention

2011 ◽  
Vol 4 (12) ◽  
pp. 2015-2026 ◽  
Author(s):  
Altaf Mohammed ◽  
Naveena B. Janakiram ◽  
Qian Li ◽  
Chang-In Choi ◽  
Yuting Zhang ◽  
...  
2013 ◽  
Vol 34 (11) ◽  
pp. 2629-2638 ◽  
Author(s):  
Elvira R.M. Bakker ◽  
Asha Mooppilmadham Das ◽  
Werner Helvensteijn ◽  
Patrick F. Franken ◽  
Sigrid Swagemakers ◽  
...  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Johanna Grinat ◽  
Julian Heuberger ◽  
Ramon Oliveira Vidal ◽  
Neha Goveas ◽  
Frauke Kosel ◽  
...  

AbstractWnt/β-catenin signaling is crucial for intestinal carcinogenesis and the maintenance of intestinal cancer stem cells. Here we identify the histone methyltransferase Mll1 as a regulator of Wnt-driven intestinal cancer. Mll1 is highly expressed in Lgr5+ stem cells and human colon carcinomas with increased nuclear β-catenin. High levels of MLL1 are associated with poor survival of colon cancer patients. The genetic ablation of Mll1 in mice prevents Wnt/β-catenin-driven adenoma formation from Lgr5+ intestinal stem cells. Ablation of Mll1 decreases the self-renewal of human colon cancer spheres and halts tumor growth of xenografts. Mll1 controls the expression of stem cell genes including the Wnt/β-catenin target gene Lgr5. Upon the loss of Mll1, histone methylation at the stem cell promoters switches from activating H3K4 tri-methylation to repressive H3K27 tri-methylation, indicating that Mll1 sustains stem cell gene expression by antagonizing gene silencing through polycomb repressive complex 2 (PRC2)-mediated H3K27 tri-methylation. Transcriptome profiling of Wnt-mutated intestinal tumor-initiating cells reveals that Mll1 regulates Gata4/6 transcription factors, known to sustain cancer stemness and to control goblet cell differentiation. Our results demonstrate that Mll1 is an essential epigenetic regulator of Wnt/β-catenin-induced intestinal tumorigenesis and cancer stemness.


2014 ◽  
Vol 42 (06) ◽  
pp. 1555-1558 ◽  
Author(s):  
Chong-Zhi Wang ◽  
Zhiyu Zhang ◽  
Samantha Anderson ◽  
Chun-Su Yuan

Natural products play an important role in cancer therapeutics, and lately more attentions have been paid to the prevention of major lethal malignancies, such as colorectal cancer (CRC). After oral ingestion, botanicals' parent compounds can be converted to their metabolites by the enteric microbiome, and these metabolites may have different bioactivities and variable bioavailability. In this study, we used an active ginseng metabolite, protopanaxadiol (PPD), as an example to assess its colon cancer preventive effect by comparing its effect with the treatment effect of fluorouracil (5-FU). A xenograft tumor nude mouse model with human colon cancer cell inoculation was used. After preventive PPD or treatment 5-FU administration with the same dose (30 mg/kg), tumor growth inhibition was evaluated by both a Xenogen bioluminescence imaging technique and manual tumor size measurement. Our data showed that preventive PPD very significantly inhibited the tumor growth compared to 5-FU (p < 0.01). Our data suggest that the PPD is a promising cancer prevention agent. More studies are needed to explore the chemopreventive actions of PPD and its potential clinical utility.


2001 ◽  
Vol 120 (5) ◽  
pp. A493-A493
Author(s):  
J HARDWICK ◽  
G VANDENBRINK ◽  
S VANDEVENTER ◽  
M PEPPELENBOSCH

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