Matches in SemOpenAlex for { <https://semopenalex.org/work/W2948115989> ?p ?o ?g. }
- W2948115989 endingPage "2152" @default.
- W2948115989 startingPage "2152" @default.
- W2948115989 abstract "Tumor suppressor p53 is mutated in about 50% of cancers. Most malignant melanomas carry wild-type p53, but p53 activity is often inhibited due to overexpression of its negative regulators Mdm2 or MdmX. We performed high throughput screening of 2448 compounds on A375 cells carrying p53 activity luciferase reporter construct to reveal compounds that promote p53 activity in melanoma. Albendazole and fenbendazole, two approved and commonly used benzimidazole anthelmintics, stimulated p53 activity and were selected for further studies. The protein levels of p53 and p21 increased upon the treatment with albendazole and fenbendazole, indicating activation of the p53–p21 pathway, while the levels of Mdm2 and MdmX decreased in melanoma and breast cancer cells overexpressing these proteins. We also observed a reduction of cell viability and changes of cellular morphology corresponding to mitotic catastrophe, i.e., G2/M cell cycle arrest of large multinucleated cells with disrupted microtubules. In summary, we established a new tool for testing the impact of small molecule compounds on the activity of p53 and used it to identify the action of benzimidazoles in melanoma cells. The drugs promoted the stability and transcriptional activity of wild-type p53 via downregulation of its negative regulators Mdm2 and MdmX in cells overexpressing these proteins. The results indicate the potential for repurposing the benzimidazole anthelmintics for the treatment of cancers overexpressing p53 negative regulators." @default.
- W2948115989 created "2019-06-14" @default.
- W2948115989 creator A5009238334 @default.
- W2948115989 creator A5015257890 @default.
- W2948115989 creator A5035207920 @default.
- W2948115989 creator A5059927382 @default.
- W2948115989 creator A5079872662 @default.
- W2948115989 date "2019-06-07" @default.
- W2948115989 modified "2023-10-05" @default.
- W2948115989 title "Benzimidazoles Downregulate Mdm2 and MdmX and Activate p53 in MdmX Overexpressing Tumor Cells" @default.
- W2948115989 cites W118091795 @default.
- W2948115989 cites W1614317053 @default.
- W2948115989 cites W1925535727 @default.
- W2948115989 cites W1973514430 @default.
- W2948115989 cites W1976295398 @default.
- W2948115989 cites W1999666865 @default.
- W2948115989 cites W2003214628 @default.
- W2948115989 cites W2007249806 @default.
- W2948115989 cites W2009234416 @default.
- W2948115989 cites W2012415856 @default.
- W2948115989 cites W2028337996 @default.
- W2948115989 cites W2030430397 @default.
- W2948115989 cites W2038596114 @default.
- W2948115989 cites W2042145670 @default.
- W2948115989 cites W2046585589 @default.
- W2948115989 cites W2083049125 @default.
- W2948115989 cites W2085881821 @default.
- W2948115989 cites W2086508126 @default.
- W2948115989 cites W2095877288 @default.
- W2948115989 cites W2105615050 @default.
- W2948115989 cites W2111150600 @default.
- W2948115989 cites W2112284988 @default.
- W2948115989 cites W2119277399 @default.
- W2948115989 cites W2123845161 @default.
- W2948115989 cites W2128290719 @default.
- W2948115989 cites W2134983040 @default.
- W2948115989 cites W2135103304 @default.
- W2948115989 cites W2148881504 @default.
- W2948115989 cites W2171910732 @default.
- W2948115989 cites W2223581935 @default.
- W2948115989 cites W2303171964 @default.
- W2948115989 cites W2473656609 @default.
- W2948115989 cites W2521851594 @default.
- W2948115989 cites W2605565637 @default.
- W2948115989 cites W2761500998 @default.
- W2948115989 cites W2765433186 @default.
- W2948115989 cites W2806295244 @default.
- W2948115989 cites W2886834231 @default.
- W2948115989 doi "https://doi.org/10.3390/molecules24112152" @default.
- W2948115989 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6600429" @default.
- W2948115989 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31181622" @default.
- W2948115989 hasPublicationYear "2019" @default.
- W2948115989 type Work @default.
- W2948115989 sameAs 2948115989 @default.
- W2948115989 citedByCount "20" @default.
- W2948115989 countsByYear W29481159892019 @default.
- W2948115989 countsByYear W29481159892020 @default.
- W2948115989 countsByYear W29481159892021 @default.
- W2948115989 countsByYear W29481159892022 @default.
- W2948115989 countsByYear W29481159892023 @default.
- W2948115989 crossrefType "journal-article" @default.
- W2948115989 hasAuthorship W2948115989A5009238334 @default.
- W2948115989 hasAuthorship W2948115989A5015257890 @default.
- W2948115989 hasAuthorship W2948115989A5035207920 @default.
- W2948115989 hasAuthorship W2948115989A5059927382 @default.
- W2948115989 hasAuthorship W2948115989A5079872662 @default.
- W2948115989 hasBestOaLocation W29481159891 @default.
- W2948115989 hasConcept C104317684 @default.
- W2948115989 hasConcept C121608353 @default.
- W2948115989 hasConcept C127561419 @default.
- W2948115989 hasConcept C185592680 @default.
- W2948115989 hasConcept C190283241 @default.
- W2948115989 hasConcept C2776192174 @default.
- W2948115989 hasConcept C2777221213 @default.
- W2948115989 hasConcept C2777658100 @default.
- W2948115989 hasConcept C29537977 @default.
- W2948115989 hasConcept C502942594 @default.
- W2948115989 hasConcept C54355233 @default.
- W2948115989 hasConcept C55493867 @default.
- W2948115989 hasConcept C62112901 @default.
- W2948115989 hasConcept C86803240 @default.
- W2948115989 hasConcept C95444343 @default.
- W2948115989 hasConcept C96232424 @default.
- W2948115989 hasConceptScore W2948115989C104317684 @default.
- W2948115989 hasConceptScore W2948115989C121608353 @default.
- W2948115989 hasConceptScore W2948115989C127561419 @default.
- W2948115989 hasConceptScore W2948115989C185592680 @default.
- W2948115989 hasConceptScore W2948115989C190283241 @default.
- W2948115989 hasConceptScore W2948115989C2776192174 @default.
- W2948115989 hasConceptScore W2948115989C2777221213 @default.
- W2948115989 hasConceptScore W2948115989C2777658100 @default.
- W2948115989 hasConceptScore W2948115989C29537977 @default.
- W2948115989 hasConceptScore W2948115989C502942594 @default.
- W2948115989 hasConceptScore W2948115989C54355233 @default.
- W2948115989 hasConceptScore W2948115989C55493867 @default.
- W2948115989 hasConceptScore W2948115989C62112901 @default.
- W2948115989 hasConceptScore W2948115989C86803240 @default.
- W2948115989 hasConceptScore W2948115989C95444343 @default.