ArticleScientific reports2019
Novel screening system revealed that intracellular cholesterol trafficking can be a good target for colon cancer prevention.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Association between the gut microbiota, inflammatory factors, and colorectal cancer: evidence from Mendelian randomization analysis.Frontiers in microbiology · 2024Article
- Theoretical basis validation and oxidative stress markers for cancer prevention clinical trials of aspirin.Scientific reports · 2023Article
- Grouped-seq for integrated phenotypic and transcriptomic screening of patient-derived tumor organoids.Nucleic acids research · 2022Article
- Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High-Fat Diet Compared to an AIN-93 Diet.Metabolites · 2021Article
- AdipoRon Attenuates Wnt Signaling by Reducing Cholesterol-Dependent Plasma Membrane Rigidity.Biophysical journal · 2020Article
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Authors and funding
10 authors.
Funding
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Abstract
In conventional research methods for cancer prevention, cell proliferation and apoptosis have been intensively targeted rather than the protection of normal or benign tumor cells from malignant transformation. In this study, we aimed to identify candidate colon cancer chemopreventive drugs based on the transcriptional activities of TCF/LEF, NF-κB and NRF2, that play important roles in the process of malignant transformation. We screened a "validated library" consisting of 1280 approved drugs to identify hit compounds that decreased TCF/LEF and NF-κB transcriptional activity and increased NRF2 transcriptional activity. Based on the evaluation of these 3 transcriptional activities, 8 compounds were identified as candidate chemopreventive drugs for colorectal cancer. One of those, itraconazole, is a clinically used anti-fungal drug and was examined in the Min mouse model of familial adenomatous polyposis. Treatment with itraconazole significantly suppressed intestinal polyp formation and the effects of itraconazole on transcriptional activities may be exerted partly through inhibition of intracellular cholesterol trafficking. This screen represents one of the first attempts to identify chemopreventive agents using integrated criteria consisting of the inhibition of TCF/LEF, NF-κB and induction of NRF2 transcriptional activity.
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