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Article

Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models

1
Department of Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences Krems, A-3500 Krems, Austria
2
Department of Dermatology, Paracelsus Medical University, A-5020 Salzburg, Austria
3
Department Life Sciences, Research Institute for Applied Bioanalytics and Drug Development, IMC University of Applied Sciences Krems, A-3500 Krems, Austria
4
Molecular Devices, LLC, A-5071 Wals-Siezenheim, Austria
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Bruno Botta, Cinzia Ingallina, Andrea Calcaterra and Deborah Quaglio
Molecules 2021, 26(3), 717; https://doi.org/10.3390/molecules26030717
Received: 23 December 2020 / Revised: 25 January 2021 / Accepted: 27 January 2021 / Published: 30 January 2021
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. View Full-Text
Keywords: quercetin; phenotypic drug screening; melanoma; 3D spheroids; Nrf2 signaling quercetin; phenotypic drug screening; melanoma; 3D spheroids; Nrf2 signaling
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MDPI and ACS Style

Hundsberger, H.; Stierschneider, A.; Sarne, V.; Ripper, D.; Schimon, J.; Weitzenböck, H.P.; Schild, D.; Jacobi, N.; Eger, A.; Atzler, J.; Klein, C.T.; Wiesner, C. Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models. Molecules 2021, 26, 717. https://doi.org/10.3390/molecules26030717

AMA Style

Hundsberger H, Stierschneider A, Sarne V, Ripper D, Schimon J, Weitzenböck HP, Schild D, Jacobi N, Eger A, Atzler J, Klein CT, Wiesner C. Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models. Molecules. 2021; 26(3):717. https://doi.org/10.3390/molecules26030717

Chicago/Turabian Style

Hundsberger, Harald, Anna Stierschneider, Victoria Sarne, Doris Ripper, Jasmin Schimon, Hans P. Weitzenböck, Dominik Schild, Nico Jacobi, Andreas Eger, Josef Atzler, Christian T. Klein, and Christoph Wiesner. 2021. "Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models" Molecules 26, no. 3: 717. https://doi.org/10.3390/molecules26030717

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