Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 1034
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3152
Function: GetPubMedArticleOutput_2016
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key regulator of cell detoxification, which maintains homoeostasis in healthy cells and promotes chemoresistance in cancer cells. Controlling the expression of this transcription factor is therefore of great interest. There are many compounds that have been shown to induce Nrf2 expression, but ligands that can inhibit Nrf2 are scant. Herein we characterise an i-motif-forming sequence downstream of the Nrf2 promoter, which we hypothesised may regulate the expression of the gene. The Nrf2 i-motif was found to be stable at near-physiological conditions. We identified small molecule ligands that interact with this i-motif structure and one significantly upregulated Nrf2 mRNA expression, and one ligand reduced Nrf2 mRNA expression in human cancer cells. This is the first example of controlling the promoter of Nrf2 by targeting DNA structures and offers an alternative mode of action for the development of compounds to improve the chemotherapeutic responsiveness of existing treatments for cancer.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1038/s42004-024-01387-w | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!