scholarly journals Polyphenol Containing Sorghum Brans Exhibit an Anti-Cancer Effect in Apc Min/+ Mice Treated with Dextran Sodium Sulfate

2021 ◽  
Vol 22 (15) ◽  
pp. 8286
Author(s):  
Seong-Ho Lee ◽  
Hee-Seop Lee ◽  
Jihye Lee ◽  
Darshika Amarakoon ◽  
Zhiyuan Lou ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cell Lines ◽  
Sodium Sulfate ◽  
Developed Countries ◽  
Tumor Formation ◽  
Dextran Sodium Sulfate ◽  
Protein Activity ◽  
Inhibition Of Proliferation ◽  
Sorghum Bran ◽  
Induced Apoptosis

Colon cancer (CC) is considered a high-risk cancer in developed countries. Its etiology is correlated with a high consumption of red meat and low consumption of plant-based foods, including whole grains. Sorghum bran is rich in polyphenols. This study aimed to determine whether different high-phenolic sorghum brans suppress tumor formation in a genetic CC rodent model and elucidate mechanisms. Tissue culture experiments used colorectal cancer cell lines SW480, HCT-116 and Caco-2 and measured protein expression, and protein activity. The animal model used in this study was APC Min+/mouse model combined with dextram sodium sulfate. High phenolic sorghum bran extract treatment resulted in the inhibition of proliferation and induced apoptosis in CC cell lines. Treatment with high phenolic sorghum bran extracts repressed TNF-α-stimulated NF-κB transactivation and IGF-1-stimulated PI3K/AKT pathway via the downregulation of β-catenin transactivation. Furthermore, high-phenolic sorghum bran extracts activated AMPK and autophagy. Feeding with high-phenolic sorghum bran for 6 weeks significantly suppressed tumor formation in an APC Min/+ dextran sodium sulfate promoted CC mouse model. Our data demonstrates the potential application of high-phenolic sorghum bran as a functional food for the prevention of CC.

Dynamic pathology for circulating free DNA in a dextran sodium sulfate colitis mouse model

2014 ◽  
Vol 30 (12) ◽  
pp. 1199-1206 ◽  
Author(s):  
Yuhki Koike ◽  
Keiichi Uchida ◽  
Koji Tanaka ◽  
Shozo Ide ◽  
Kohei Otake ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sodium Sulfate ◽  
Dextran Sodium Sulfate ◽  
Circulating Free Dna ◽  
Free Dna

Targeting mutant p53 with PK11007: A new approach for the treatment of patients with triple-negative breast cancer?

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14099-e14099 ◽  
Author(s):  
Naoise C Synnott ◽  
Matthias R Bauer ◽  
Stephen F. Madden ◽  
Alyson M. Murray ◽  
Rut Klinger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
P53 Protein ◽  
Mutant P53 ◽  
Inhibition Of Proliferation ◽  
Tnbc Cell ◽  
Induced Apoptosis

e14099 Background:The identification of a targeted therapy for patients with triple-negative breast cancer (TNBC) is one of the most urgent needs in breast cancer therapeutics. Since the p53 gene is mutated in approximately 80% of TNBC patients, it is a potential therapeutic target for this form of breast cancer. PK11007 is a 2-sulfonypyrimidine that stabilizes and reactivates mutant p53 (Bauer et al, PNAS 2016). The compound recently was reported to preferentially decrease viability in p53-compromised cancer cells. The aim of this investigation was to evaluate PK11007 as a potential new treatment for TNBC. Methods: Cell viability was determined using the MTT assay. Apoptosis was detected using Annexin V Apoptosis Detection Kit. Migration was determined by Transwell migration assay. Knockdowns of p53 protein were carried out using predesigned Flexitube sequences (Qiagen). Results: IC50 values for inhibition of proliferation by PK11007 in the panel of 17 breast cell lines ranged from 2.3 to 42.2 μM. There were significantly lower IC50values for TNBC than for non-TNBC cell lines (p = 0.03) and for p53-mutated cell lines compared with p53 WT cells (p = 0.003). Response to PK11007 however, was independent of ER or HER2 status of the cells. In addition, PK11007 induced apoptosis and inhibited migration in p53 mutant cell lines. Using RNAseq and gene ontogeny analysis, we found that PK11007 altered the expression of genes enriched in pathways involved in regulated cell death, regulation of apoptosis, signal transduction, protein refolding and locomotion. To establish if PK11007 acts by targeting mutant p53, we used siRNA to knockdown p53 in 3 p53-mutated TNBC cell lines. Reduction in p53 protein levels resulted in a significant decrease in the growth inhibitory effects of PK11007, in all 3 cell lines investigated, suggesting that PK11007 mediates growth inhibition via p53. The observations that PK11007 inhibited cell growth, induced apoptosis, blocked cell migration and altered genes involved in cell death, are all consistent with the ability of PK11007 to activate mutant p53. Conclusions: Based on our data, we conclude that targeting mutant p53 with PK11007 is a potential approach for treating p53-mutated TNBC.

ASPP2 Haploinsufficiency Promotes Tumor Formation in a Mouse Model.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4333-4333
Author(s):  
Kerstin M. Kampa ◽  
Jared D. Acoba ◽  
Dexi Chen ◽  
Kelly Beemer ◽  
Joel Gay ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Mouse Model ◽  
B Cell Lymphoma ◽  
Tumor Formation ◽  
Rank Test ◽  
Serum Starvation ◽  
Free Survival ◽  
Induced Apoptosis ◽  
Tumor Types

Abstract ASPP2 interacts with the tumor suppressor protein p53 and promotes damage-induced apoptosis in part through stimulation of p53-mediated apoptosis. We have previously demonstrated that low ASPP2 levels correlate with poor clinical outcome in patients with diffuse large B-cell lymphoma treated with anthracycline-based chemotherapy. Moreover, reduced ASPP2 expression has been demonstrated in other tumor types. These findings led us to hypothesize that ASPP2 may function as a tumor suppressor. To further explore this, we targeted the ASPP2 allele in a mouse by homologous recombination using a knockout vector that replaced exons 10–17 with a neoR gene. Two separate ES clones were used for blastocyst injections to generate several chimeras that were used to generate ASPP2 heterozygous mice. ASPP2+/− mice appear developmentally normal and reproduce. However ASPP2−/− mice could not be generated. Genotype analysis as early as Ed 6.5 did not detect ASPP2−/− embryos---which implies an early embryonic lethal defect in the homozygote. ASPP2+/− (n=135) and ASPP2+/+ (n=63) sibling mice were observed for spontaneous tumor formation. Overall median tumor-free survival was 117 weeks in the ASPP2+/− mice verses 125 weeks in the ASPP2+/+mice (p = 0.035 log-rank test). Overall tumor incidence (at 115 weeks) for ASPP2+/− and ASPP2+/+ mice was 43% and 22%, respectively. The incidence of tumor types, from all tumors detected, was similar between ASPP2+/− and ASPP2+/+ mice: 34% versus 33% (lymphoma), 18% versus 14% (sarcoma), and 47% versus 52% (carcinoma), respectively. Compound p53+/−;ASPP2+/− mice did not exhibit accelerated tumor formation relative to p53+/−;ASPP2+/+ mice. Additionally, a tet-Myc:ASPP2+/− lymphoma mouse model did not exhibit accelerated lymphomagenesis. However, preliminary data suggests that ASPP2+/− mice may have an increased incidence of irradiation-induced leukemia/lymphoma when compared to ASPP2+/+ mice, and confirmatory studies are ongoing. In response to ionizing radiation, doxorubicin, or serum-starvation, preliminary analysis reveals a G0/G1 checkpoint defect in ASPP2+/− MEFs compared to ASPP2+/+ MEFs. Our results provide in vivo evidence that ASPP2 can function as a tumor suppressor. Further studies are underway to determine the mechanism of this observation.

scholarly journals Effects of Selenium on Colon Carcinogenesis Induced by Azoxymethane and Dextran Sodium Sulfate in Mouse Model with High-Iron Diet

2011 ◽  
Vol 27 (1) ◽  
pp. 9 ◽  
Author(s):  
Jun-Hyeong Kim ◽  
Jin-Joo Hue ◽  
Bong Su Kang ◽  
Hyunji Park ◽  
Sang Yoon Nam ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sodium Sulfate ◽  
Colon Carcinogenesis ◽  
Dextran Sodium Sulfate ◽  
High Iron
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