Hyaluronic Acid Nanohydrogel Loaded With Quercetin Alone or in Combination to a Macrolide Derivative of Rapamycin RAD001 (Everolimus) as a New Treatment for Hormone-Responsive Human Breast Cancer
| Autor: | Vincenzo, Quagliariello, Rosario Vincenzo, Iaffaioli, Emilia, Armenia, Ottavia, Clemente, Manlio, Barbarisi, Guglielmo, Nasti, Massimiliano, Berretta, Alessandro, Ottaiano, Alfonso, Barbarisi |
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| Přispěvatelé: | Quagliariello, V, Iaffaioli, R. V, Armenia, E, Clemente, O, Barbarisi, Manlio, Nasti, Gennaro, Berretta, M, Ottaiano, A, Barbarisi, Alfonso |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Vascular Endothelial Growth Factor A
Neoplasms Hormone-Dependent Cell Survival Drug Compounding Anti-Inflammatory Agents Apoptosis Breast Neoplasms quercetin Necrosis breast cancer Antineoplastic Combined Chemotherapy Protocols hyaluronic acid Humans Everolimus Drug Carriers Dose-Response Relationship Drug Interleukins everolimu Drug Synergism Hydrogels nanohydrogel Drug Combinations Hyaluronan Receptors Matrix Metalloproteinase 9 MCF-7 Cells Matrix Metalloproteinase 2 Nanoparticles Female Reactive Oxygen Species Signal Transduction |
| Popis: | The aim of this study is based on the evaluation of anticancer, anti-inflammatory activities, and cellular uptake of hyaluronic acid nanohydrogel of quercetin tested alone and in combination to a macrolide derivative of rapamycin RAD001 (everolimus) on hormone-responsive breast cancer cell line MCF-7. Biological investigations were focused on the receptor mediated cellular internalization of the nanohydrogel and its abilities to reduce secretion of several cytokines (IL-8, IL-6, IL-19), VEGF, and metalloproteases (MMP-2, MMP-9) under pro-inflammatory conditions. Nanohydrogel show a CD44 dependent endocytosis with evident time dependent cytoplasmatic accumulation with abilities to reduce secretion of all cytokines of ∼60% compared to untreated cells. Combination of formulated quercetin and everolimus leads to a synergistic cytotoxic effects with a Combination Index of 0.38. These results highlights the importance of synergistic effect of the hyaluronic acid nanohydrogel of quercetin with everolimus in the regulation of human breast cancer cell proliferation and emphasize the antitumor and anti-inflammatory properties of the nanocarrier. J. Cell. Physiol. 232: 2063–2074, 2017. © 2016 Wiley Periodicals, Inc. The aim of this study is based on the evaluation of anticancer, anti-inflammatory activities, and cellular uptake of hyaluronic acid nanohydrogel of quercetin tested alone and in combination to a macrolide derivative of rapamycin RAD001 (everolimus) on hormone-responsive breast cancer cell line MCF-7. Biological investigations were focused on the receptor mediated cellular internalization of the nanohydrogel and its abilities to reduce secretion of several cytokines (IL-8, IL-6, IL-19), VEGF, and metalloproteases (MMP-2, MMP-9) under pro-inflammatory conditions. Nanohydrogel show a CD44 dependent endocytosis with evident time dependent cytoplasmatic accumulation with abilities to reduce secretion of all cytokines of ∼60% compared to untreated cells. Combination of formulated quercetin and everolimus leads to a synergistic cytotoxic effects with a Combination Index of 0.38. These results highlights the importance of synergistic effect of the hyaluronic acid nanohydrogel of quercetin with everolimus in the regulation of human breast cancer cell proliferation and emphasize the antitumor and anti-inflammatory properties of the nanocarrier. J. Cell. Physiol. 232: 2063–2074, 2017. © 2016 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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