Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hundsberger, Harald, Stierschneider, Anna, Sarne, Victoria, Ripper, Doris, Schimon, Jasmin, Weitzenböck, Hans Peter, Schild, Dominik, Jacobi, Nico, Eger, Andreas, Atzler, Josef, Klein, Christian T., Wiesner, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866537/
https://www.ncbi.nlm.nih.gov/pubmed/33573155
http://dx.doi.org/10.3390/molecules26030717
_version_ 1783648098313043968
author Hundsberger, Harald
Stierschneider, Anna
Sarne, Victoria
Ripper, Doris
Schimon, Jasmin
Weitzenböck, Hans Peter
Schild, Dominik
Jacobi, Nico
Eger, Andreas
Atzler, Josef
Klein, Christian T.
Wiesner, Christoph
author_facet Hundsberger, Harald
Stierschneider, Anna
Sarne, Victoria
Ripper, Doris
Schimon, Jasmin
Weitzenböck, Hans Peter
Schild, Dominik
Jacobi, Nico
Eger, Andreas
Atzler, Josef
Klein, Christian T.
Wiesner, Christoph
author_sort Hundsberger, Harald
collection PubMed
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.
format Online
Article
Text
id pubmed-7866537
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-78665372021-02-07 Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models Hundsberger, Harald Stierschneider, Anna Sarne, Victoria Ripper, Doris Schimon, Jasmin Weitzenböck, Hans Peter Schild, Dominik Jacobi, Nico Eger, Andreas Atzler, Josef Klein, Christian T. Wiesner, Christoph Molecules Article 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. MDPI 2021-01-30 /pmc/articles/PMC7866537/ /pubmed/33573155 http://dx.doi.org/10.3390/molecules26030717 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hundsberger, Harald
Stierschneider, Anna
Sarne, Victoria
Ripper, Doris
Schimon, Jasmin
Weitzenböck, Hans Peter
Schild, Dominik
Jacobi, Nico
Eger, Andreas
Atzler, Josef
Klein, Christian T.
Wiesner, Christoph
Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866537/
https://www.ncbi.nlm.nih.gov/pubmed/33573155
http://dx.doi.org/10.3390/molecules26030717
work_keys_str_mv AT hundsbergerharald concentrationdependentproandantitumoractivitiesofquercetininhumanmelanomaspheroidscomparativeanalysisof2dand3dcellculturemodels
AT stierschneideranna concentrationdependentproandantitumoractivitiesofquercetininhumanmelanomaspheroidscomparativeanalysisof2dand3dcellculturemodels
AT sarnevictoria concentrationdependentproandantitumoractivitiesofquercetininhumanmelanomaspheroidscomparativeanalysisof2dand3dcellculturemodels
AT ripperdoris concentrationdependentproandantitumoractivitiesofquercetininhumanmelanomaspheroidscomparativeanalysisof2dand3dcellculturemodels
AT schimonjasmin concentrationdependentproandantitumoractivitiesofquercetininhumanmelanomaspheroidscomparativeanalysisof2dand3dcellculturemodels
AT weitzenbockhanspeter concentrationdependentproandantitumoractivitiesofquercetininhumanmelanomaspheroidscomparativeanalysisof2dand3dcellculturemodels
AT schilddominik concentrationdependentproandantitumoractivitiesofquercetininhumanmelanomaspheroidscomparativeanalysisof2dand3dcellculturemodels
AT jacobinico concentrationdependentproandantitumoractivitiesofquercetininhumanmelanomaspheroidscomparativeanalysisof2dand3dcellculturemodels
AT egerandreas concentrationdependentproandantitumoractivitiesofquercetininhumanmelanomaspheroidscomparativeanalysisof2dand3dcellculturemodels
AT atzlerjosef concentrationdependentproandantitumoractivitiesofquercetininhumanmelanomaspheroidscomparativeanalysisof2dand3dcellculturemodels
AT kleinchristiant concentrationdependentproandantitumoractivitiesofquercetininhumanmelanomaspheroidscomparativeanalysisof2dand3dcellculturemodels
AT wiesnerchristoph concentrationdependentproandantitumoractivitiesofquercetininhumanmelanomaspheroidscomparativeanalysisof2dand3dcellculturemodels