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A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth
Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylace...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157022/ https://www.ncbi.nlm.nih.gov/pubmed/34067547 http://dx.doi.org/10.3390/ijms22105255 |
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author | Chimento, Adele Santarsiero, Anna Iacopetta, Domenico Ceramella, Jessica De Luca, Arianna Infantino, Vittoria Parisi, Ortensia Ilaria Avena, Paola Bonomo, Maria Grazia Saturnino, Carmela Sinicropi, Maria Stefania Pezzi, Vincenzo |
author_facet | Chimento, Adele Santarsiero, Anna Iacopetta, Domenico Ceramella, Jessica De Luca, Arianna Infantino, Vittoria Parisi, Ortensia Ilaria Avena, Paola Bonomo, Maria Grazia Saturnino, Carmela Sinicropi, Maria Stefania Pezzi, Vincenzo |
author_sort | Chimento, Adele |
collection | PubMed |
description | Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer. |
format | Online Article Text |
id | pubmed-8157022 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81570222021-05-28 A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth Chimento, Adele Santarsiero, Anna Iacopetta, Domenico Ceramella, Jessica De Luca, Arianna Infantino, Vittoria Parisi, Ortensia Ilaria Avena, Paola Bonomo, Maria Grazia Saturnino, Carmela Sinicropi, Maria Stefania Pezzi, Vincenzo Int J Mol Sci Article Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer. MDPI 2021-05-17 /pmc/articles/PMC8157022/ /pubmed/34067547 http://dx.doi.org/10.3390/ijms22105255 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chimento, Adele Santarsiero, Anna Iacopetta, Domenico Ceramella, Jessica De Luca, Arianna Infantino, Vittoria Parisi, Ortensia Ilaria Avena, Paola Bonomo, Maria Grazia Saturnino, Carmela Sinicropi, Maria Stefania Pezzi, Vincenzo A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth |
title | A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth |
title_full | A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth |
title_fullStr | A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth |
title_full_unstemmed | A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth |
title_short | A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth |
title_sort | phenylacetamide resveratrol derivative exerts inhibitory effects on breast cancer cell growth |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157022/ https://www.ncbi.nlm.nih.gov/pubmed/34067547 http://dx.doi.org/10.3390/ijms22105255 |
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