Phenethyl Isothiocyanate Inhibited Tumor Migration and Invasion via Suppressing Multiple Signal Transduction Pathways in Human Colon Cancer HT29 Cells

2010 ◽  
Vol 58 (20) ◽  
pp. 11148-11155 ◽  
Author(s):  
Kuang-Chi Lai ◽  
Shu-Chun Hsu ◽  
Chao-Lin Kuo ◽  
Siu-Wan Ip ◽  
Jai-Sing Yang ◽  
...  



2020 ◽  
Vol 48 (12) ◽  
pp. 030006052097145
Author(s):  
Jie Pan ◽  
Zongbin Xu ◽  
Meifang Xu ◽  
Xiaoyan Lin ◽  
Bingqiang Lin ◽  
...  

Background This study aimed to evaluate the role and the underlying mechanisms of Forkhead box A1 (encoded by FOXA1) in colon cancer. Methods We analyzed FOXA1 mRNA and protein expression in colon cancer tissues and cell lines. We also silenced FOXA1 expression in HCT116 and SW480 cells to evaluate the effects on cell proliferation, cell cycle, migration, and invasion by using MTT, colony formation, flow cytometry, and the Transwell assay, respectively. Results FOXA1 immunostaining was higher in colon cancer tissues than adjacent healthy tissues. FOXA1 mRNA and protein expression was significantly increased in human colon cancer cells compared with a normal colonic cell line. FOXA1 expression was also significantly higher in colorectal cancer tissues from TCGA data sets and was associated with worse prognosis in the R2 database. FOXA1 expression was negatively correlated with the extent of its methylation, and its knockdown reduced proliferation, migration, and invasion, and induced G2/M phase arrest in HCT116 and SW480 cells by suppressing the phosphatase and tensin homolog/Akt signaling pathway and inhibiting epithelial–mesenchymal transition. Conclusion FOXA1 may act as an oncogene in colon cancer tumorigenesis and development.





2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Jiafeng Tong ◽  
Ying Shen ◽  
Zhenghua Zhang ◽  
Ye Hu ◽  
Xu Zhang ◽  
...  

Abstract Colon cancer is a leading cause of cancer-related deaths worldwide. The epithelial-mesenchymal transition (EMT) plays an important role in tumor metastasis of colon cancer. We first evaluated the effects of EMT-related transcription factors on the prognosis of colon cancer through analysis the data obtained from The Cancer Genome Atlas (TCGA). And then we screened a series of Chinese medicine monomers to find effect EMT inhibitors. First, Snail is a more important EMT transcription factors for colon cancer prognosis, compared with Twist and Slug. Then, we found that apigenin effectively inhibits the activity of Snail. Apigenin could inhibit the EMT, migration, and invasion of human colon cancer cells in vitro and in vivo through the NF-κB/Snail pathway. Snail is a key regulator of EMT in colon cancer and Snail inhibitor apigenin may be a therapeutic application for patients with colon cancer.



2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Seong-Ho Lee ◽  
Jihye Lee ◽  
Thomas Herald ◽  
Sarah Cox ◽  
Leela Noronha ◽  
...  

Abstract Objectives Colon cancer is one of leading causes of cancer mortality worldwide. Sorghum is the fifth most largely cultivated crop for human diet in the world. Most sorghum varieties contain high content of phenolic compounds. The objective of the current study is to evaluate the anti-cancer properties of a novel high phenolic sorghum bran extract prepared under 70% ethanol with 5% citric acid solvent. Methods High phenolic sorghum, accession number PI570481, was grown in Puerto Vallarta, Mexico winter nursery during the 2018 and high phenolic sorghum bran extract was prepared using 70% ethanol with 5% citric acid solvent at room temperature for 2 hours. Human colon cancer cell lines (HCT15, SW480, HCT116 and HT-29) were treated with different doses of high phenolic sorghum bran extract. Cell proliferation and apoptosis was measured using MTS assay and Alexa Fluor 488 Annexin V/Dead Cell Apoptosis system, respectively. Distribution of cell cycle was measured Texas Red channel using BD LSRFortessa system. Cell migration and invasion was measured using wound healing assay and Matrigel, respectively. The luciferase activity of reporter genes was measured using a dual-luciferase assay and Western blot was performed to measure expression of cancer phenotype-associated proteins. Results Cell proliferation was inhibited and apoptosis was induced in the human colon cancer cells treated with high phenolic sorghum bran extract in a dose-dependent manner. High phenolic sorghum bran extract led to S phage arrest. Cell migration and invasion was also repressed in the human colon cancer cells treated with high phenolic sorghum bran extract. The change of cancer phenotypes was associated with up- or down-regulation of regulatory genes. Conclusions The present study expands our understanding on the potential use of high phenolic sorghum bran for prevention of human colon cancer. Funding Sources Cooperative Agreement grant from USDA-ARS to S-HL.



2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Kyeong-Ah Jung ◽  
Mi-Kyoung Kwak

Nuclear factor erythroid 2-related factor 2 (NRF2) is the transcription factor that regulates an array of antioxidant/detoxifying genes for cellular defense. The conformational changes of Kelch-like ECH-associated protein 1 (KEAP1), a cytosolic repressor protein of NRF2, by various stimuli result in NRF2 liberation and accumulation in the nucleus. In the present study, we aimed to investigate the effect ofKEAP1knockdown on NRF2 target gene expression and its toxicological implication using human colon cancer cells. The stableKEAP1-knockdown HT29 cells exhibit elevated levels of NRF2 and its target gene expressions. In particular, the mRNA levels of aldo-keto reductases (AKR1C1, 1C2, 1C3, 1B1, and 1B10) were substantially increased inKEAP1silenced HT29 cells. These differential AKRs expressions appear to contribute to protection against oxidative stress. TheKEAP1-knockdown cells were relatively more resistant to hydrogen peroxide (H2O2) and 4-hydroxynonenal (4HNE) compared to the control cells. Accordantly, we observed accumulation of 4HNE protein adducts in H2O2- or 4HNE-treated control cells, whereasKEAP1-knockdown cells did not increase adduct formation. The treatment ofKEAP1-silenced cells with AKR1C inhibitor flufenamic acid increased 4HNE-induced cellular toxicity and protein adduct formation. Taken together, these results indicate that AKRs, which are NRF2-dependent highly inducible gene clusters, play a role in NRF2-mediated cytoprotection against lipid peroxide toxicity.





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