A PHP Error was encountered

Severity: Warning

Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests

Filename: helpers/my_audit_helper.php

Line Number: 143

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 994
Function: getPubMedXML

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3134
Function: GetPubMedArticleOutput_2016

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

Enhanced anticancer effect of thymidylate synthase dimer disrupters by promoting intracellular accumulation. | LitMetric

AI Article Synopsis

  • Thymidylate synthase (TS) is important for DNA synthesis and repair, and its overexpression contributes to drug resistance in cancer cells, particularly in ovarian and colon cancers.
  • This study found that novel TS dimer disrupters (Ddis) were more effective at killing cancer cells when used alongside inhibitors of drug efflux proteins, which prevent the drugs from leaving the cells.
  • The research also utilized a protein transfection agent to enhance the uptake of these Ddis, leading to reduced TS protein levels and disruptions in the cell cycle, indicating potential for improved cancer therapies.

Article Abstract

Introduction: Thymidylate synthase (TS) plays a crucial role in cellular growth, proliferation, DNA synthesis, and repair, thus gaining attention for targeted therapies in cancer. TS overexpression and the altered pharmacokinetics of anti-TS drugs are among the most prominent causes of cellular resistance. Decreased drug influx and/or efficient efflux result in reduced drug access to the intracellular targets.

Results: In this study, we have evaluated and demonstrated the increased cytotoxic efficacy of novel TS dimer disrupters (Ddis) in the presence of specific inhibitors of drug efflux protein pumps in ovarian and colon cancer cells, suggesting that these compounds are substrates of the cellular drug extruders. A second strategy adopted to favor intracellular accumulation was to employ, as a drug delivery system, a molecular tool able to help less lipophilic compounds to cross the cell membrane. The Ddis were delivered through the SAINT-Protein transfection agent. The observed cell-killing effects agreed with the reduction of TS protein level and cell cycle perturbation.

Conclusion: Overall, this preclinical study suggests that the innovative TS dimer disrupters can be optimized by increasing their intracellular accumulation by both inhibiting their outflow and/or enhancing cellular uptake.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602703PMC
http://dx.doi.org/10.3389/fphar.2024.1477318DOI Listing

Publication Analysis

Top Keywords

dimer disrupters
12
intracellular accumulation
12
thymidylate synthase
8
drug
5
enhanced anticancer
4
anticancer thymidylate
4
synthase dimer
4
disrupters promoting
4
intracellular
4
promoting intracellular
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: