Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models
Quercetin, a dietary flavonoid found in fruits and vegetables, has been described as a substance with many anti-cancer properties in a variety of preclinical investigations. In the present study, we demonstrate that 2D and 3D melanoma models exhibit not only different sensitivities to quercetin, but...
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2021-01-01
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author | Harald Hundsberger Anna Stierschneider Victoria Sarne Doris Ripper Jasmin Schimon Hans Peter Weitzenböck Dominik Schild Nico Jacobi Andreas Eger Josef Atzler Christian T. Klein Christoph Wiesner |
author_facet | Harald Hundsberger Anna Stierschneider Victoria Sarne Doris Ripper Jasmin Schimon Hans Peter Weitzenböck Dominik Schild Nico Jacobi Andreas Eger Josef Atzler Christian T. Klein Christoph Wiesner |
author_sort | Harald Hundsberger |
collection | DOAJ |
description | Quercetin, a dietary flavonoid found in fruits and vegetables, has been described as a substance with many anti-cancer properties in a variety of preclinical investigations. In the present study, we demonstrate that 2D and 3D melanoma models exhibit not only different sensitivities to quercetin, but also opposite, cancer-promoting effects when metastatic melanoma spheroids are treated with quercetin. Higher concentrations of quercetin reduce melanoma growth in three tested cell lines, whereas low concentrations induce the opposite effect in metastatic melanoma spheroids but not in the non-metastatic cell line. High (>12.5 µM) or low (<6.3 µM) quercetin concentrations decrease or enhance cell viability, spheroid size, and cell proliferation, respectively. Additionally, melanoma cells cultivated in 2D already show significant caspase 3 activity at very low concentrations (>0.4 µM), whereas in 3D spheroids apoptotic cells, caspase 3 activity can only be detected in concentrations ≥12.5 µM. Further, we show that the tumor promoting or repressing effect in the 3D metastatic melanoma spheroids are likely to be elicited by a precisely controlled regulation of Nrf2/ARE-mediated cytoprotective genes, as well as ERK and NF-κB phosphorylation. According to the results obtained here, further studies are needed to better characterize the mechanisms of action underlying the pro- and anti-carcinogenic effects of quercetin on human melanomas. |
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spelling | doaj.art-4fb9df26e41e4fa39ded70e0d754c9b02023-12-03T15:20:14ZengMDPI AGMolecules1420-30492021-01-0126371710.3390/molecules26030717Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture ModelsHarald Hundsberger0Anna Stierschneider1Victoria Sarne2Doris Ripper3Jasmin Schimon4Hans Peter Weitzenböck5Dominik Schild6Nico Jacobi7Andreas Eger8Josef Atzler9Christian T. Klein10Christoph Wiesner11Department of Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences Krems, A-3500 Krems, AustriaDepartment of Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences Krems, A-3500 Krems, AustriaDepartment of Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences Krems, A-3500 Krems, AustriaDepartment of Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences Krems, A-3500 Krems, AustriaDepartment of Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences Krems, A-3500 Krems, AustriaDepartment of Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences Krems, A-3500 Krems, AustriaDepartment of Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences Krems, A-3500 Krems, AustriaDepartment Life Sciences, Research Institute for Applied Bioanalytics and Drug Development, IMC University of Applied Sciences Krems, A-3500 Krems, AustriaDepartment of Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences Krems, A-3500 Krems, AustriaMolecular Devices, LLC, A-5071 Wals-Siezenheim, AustriaDepartment of Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences Krems, A-3500 Krems, AustriaDepartment of Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences Krems, A-3500 Krems, AustriaQuercetin, a dietary flavonoid found in fruits and vegetables, has been described as a substance with many anti-cancer properties in a variety of preclinical investigations. In the present study, we demonstrate that 2D and 3D melanoma models exhibit not only different sensitivities to quercetin, but also opposite, cancer-promoting effects when metastatic melanoma spheroids are treated with quercetin. Higher concentrations of quercetin reduce melanoma growth in three tested cell lines, whereas low concentrations induce the opposite effect in metastatic melanoma spheroids but not in the non-metastatic cell line. High (>12.5 µM) or low (<6.3 µM) quercetin concentrations decrease or enhance cell viability, spheroid size, and cell proliferation, respectively. Additionally, melanoma cells cultivated in 2D already show significant caspase 3 activity at very low concentrations (>0.4 µM), whereas in 3D spheroids apoptotic cells, caspase 3 activity can only be detected in concentrations ≥12.5 µM. Further, we show that the tumor promoting or repressing effect in the 3D metastatic melanoma spheroids are likely to be elicited by a precisely controlled regulation of Nrf2/ARE-mediated cytoprotective genes, as well as ERK and NF-κB phosphorylation. According to the results obtained here, further studies are needed to better characterize the mechanisms of action underlying the pro- and anti-carcinogenic effects of quercetin on human melanomas.https://www.mdpi.com/1420-3049/26/3/717quercetinphenotypic drug screeningmelanoma3D spheroidsNrf2 signaling |
spellingShingle | Harald Hundsberger Anna Stierschneider Victoria Sarne Doris Ripper Jasmin Schimon Hans Peter Weitzenböck Dominik Schild Nico Jacobi Andreas Eger Josef Atzler Christian T. Klein Christoph Wiesner Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models Molecules quercetin phenotypic drug screening melanoma 3D spheroids Nrf2 signaling |
title | Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models |
title_full | Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models |
title_fullStr | Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models |
title_full_unstemmed | Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models |
title_short | Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models |
title_sort | concentration dependent pro and antitumor activities of quercetin in human melanoma spheroids comparative analysis of 2d and 3d cell culture models |
topic | quercetin phenotypic drug screening melanoma 3D spheroids Nrf2 signaling |
url | https://www.mdpi.com/1420-3049/26/3/717 |
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