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Identification of the Plant Compound Geraniin as a Novel Hsp90 Inhibitor
Besides its function in normal cellular growth, the molecular chaperone heat shock protein 90 (Hsp90) binds to a large number of client proteins required for promoting cancer cell growth and/or survival. In an effort to discover new small molecules able to inhibit the Hsp90 ATPase and chaperoning ac...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774728/ https://www.ncbi.nlm.nih.gov/pubmed/24066128 http://dx.doi.org/10.1371/journal.pone.0074266 |
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author | Vassallo, Antonio Vaccaro, Maria Carmela De Tommasi, Nunziatina Dal Piaz, Fabrizio Leone, Antonella |
author_facet | Vassallo, Antonio Vaccaro, Maria Carmela De Tommasi, Nunziatina Dal Piaz, Fabrizio Leone, Antonella |
author_sort | Vassallo, Antonio |
collection | PubMed |
description | Besides its function in normal cellular growth, the molecular chaperone heat shock protein 90 (Hsp90) binds to a large number of client proteins required for promoting cancer cell growth and/or survival. In an effort to discover new small molecules able to inhibit the Hsp90 ATPase and chaperoning activities, we screened, by a surface plasmon resonance assay, a small library including different plant polyphenols. The ellagitannin geraniin, was identified as the most promising molecule, showing a binding affinity to Hsp90α similar to that of 17-(allylamino)-17-demethoxygeldanamycin (17AGG). Geraniin was able to inhibit in vitro the Hsp90α ATPase activity in a dose−dependent manner, with an inhibitory efficiency comparable to that measured for 17-AAG. In addition, this compound compromised the chaperone activity of Hsp90α, monitored by the citrate synthase thermal induced aggregation assay. Geraniin decreased the viability of HeLa and Jurkat cell lines and caused an arrest in G(2)/M phase. We also proved that following exposure to different concentrations of geraniin, the level of expression of the client proteins c-Raf, pAkt, and EGFR was strongly down−regulated in both the cell lines. These results, along with the finding that geraniin did not exert any appreciable cytotoxicity on normal cells, encourage further studies on this compound as a promising chemical scaffold for the design of new Hsp90 inhibitors. |
format | Online Article Text |
id | pubmed-3774728 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37747282013-09-24 Identification of the Plant Compound Geraniin as a Novel Hsp90 Inhibitor Vassallo, Antonio Vaccaro, Maria Carmela De Tommasi, Nunziatina Dal Piaz, Fabrizio Leone, Antonella PLoS One Research Article Besides its function in normal cellular growth, the molecular chaperone heat shock protein 90 (Hsp90) binds to a large number of client proteins required for promoting cancer cell growth and/or survival. In an effort to discover new small molecules able to inhibit the Hsp90 ATPase and chaperoning activities, we screened, by a surface plasmon resonance assay, a small library including different plant polyphenols. The ellagitannin geraniin, was identified as the most promising molecule, showing a binding affinity to Hsp90α similar to that of 17-(allylamino)-17-demethoxygeldanamycin (17AGG). Geraniin was able to inhibit in vitro the Hsp90α ATPase activity in a dose−dependent manner, with an inhibitory efficiency comparable to that measured for 17-AAG. In addition, this compound compromised the chaperone activity of Hsp90α, monitored by the citrate synthase thermal induced aggregation assay. Geraniin decreased the viability of HeLa and Jurkat cell lines and caused an arrest in G(2)/M phase. We also proved that following exposure to different concentrations of geraniin, the level of expression of the client proteins c-Raf, pAkt, and EGFR was strongly down−regulated in both the cell lines. These results, along with the finding that geraniin did not exert any appreciable cytotoxicity on normal cells, encourage further studies on this compound as a promising chemical scaffold for the design of new Hsp90 inhibitors. Public Library of Science 2013-09-16 /pmc/articles/PMC3774728/ /pubmed/24066128 http://dx.doi.org/10.1371/journal.pone.0074266 Text en © 2013 Vassallo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Vassallo, Antonio Vaccaro, Maria Carmela De Tommasi, Nunziatina Dal Piaz, Fabrizio Leone, Antonella Identification of the Plant Compound Geraniin as a Novel Hsp90 Inhibitor |
title | Identification of the Plant Compound Geraniin as a Novel Hsp90 Inhibitor |
title_full | Identification of the Plant Compound Geraniin as a Novel Hsp90 Inhibitor |
title_fullStr | Identification of the Plant Compound Geraniin as a Novel Hsp90 Inhibitor |
title_full_unstemmed | Identification of the Plant Compound Geraniin as a Novel Hsp90 Inhibitor |
title_short | Identification of the Plant Compound Geraniin as a Novel Hsp90 Inhibitor |
title_sort | identification of the plant compound geraniin as a novel hsp90 inhibitor |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774728/ https://www.ncbi.nlm.nih.gov/pubmed/24066128 http://dx.doi.org/10.1371/journal.pone.0074266 |
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