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Autophagy Inhibitor Chloroquine Enhanced the Cell Death Inducing Effect of the Flavonoid Luteolin in Metastatic Squamous Cell Carcinoma Cells

BACKGROUND: Flavonoids are widely proposed as very interesting compounds with possible chemopreventive and therapeutic capacities. METHODS & RESULTS: In this study, we showed that in vitro treatment with the flavonoid Luteolin induced caspase-dependent cell death in a model of human cutaneous sq...

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Autores principales: Verschooten, Lien, Barrette, Kathleen, Van Kelst, Sofie, Rubio Romero, Noemí, Proby, Charlotte, De Vos, Rita, Agostinis, Patrizia, Garmyn, Marjan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482182/
https://www.ncbi.nlm.nih.gov/pubmed/23110223
http://dx.doi.org/10.1371/journal.pone.0048264
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author Verschooten, Lien
Barrette, Kathleen
Van Kelst, Sofie
Rubio Romero, Noemí
Proby, Charlotte
De Vos, Rita
Agostinis, Patrizia
Garmyn, Marjan
author_facet Verschooten, Lien
Barrette, Kathleen
Van Kelst, Sofie
Rubio Romero, Noemí
Proby, Charlotte
De Vos, Rita
Agostinis, Patrizia
Garmyn, Marjan
author_sort Verschooten, Lien
collection PubMed
description BACKGROUND: Flavonoids are widely proposed as very interesting compounds with possible chemopreventive and therapeutic capacities. METHODS & RESULTS: In this study, we showed that in vitro treatment with the flavonoid Luteolin induced caspase-dependent cell death in a model of human cutaneous squamous cell carcinoma (SCC) derived cells, representing a matched pair of primary tumor and its metastasis. Notably, no cytotoxic effects were observed in normal human keratinocytes when treated with similar doses of Luteolin. Luteolin-induced apoptosis was accompanied by inhibition of AKT signaling, and sensitivity decreased with tumor progression, as the primary MET1 SCC cells were considerably more sensitive to Luteolin than the isogenic metastatic MET4 cells. Extensive intracellular vacuolization was observed in Luteolin-treated MET4 cells, which were characterized as acidic lysosomal vacuoles, suggesting the involvement of autophagy. Transmission electron microscopy, mRFP-GFP-LC3 assay and p62 protein degradation, confirmed that Luteolin stimulated the autophagic process in the metastatic MET4 cells. Blocking autophagy using chloroquine magnified Luteolin-induced apoptosis in the metastatic SCC cells. CONCLUSION: Together, these results suggest that Luteolin has the capacity to induce selectively apoptotic cell death both in primary cutaneous SCC cells and in metastatic SCC cells in combination with chloroquine, an inhibitor of autophagosomal degradation. Hence, Luteolin might be a promising agent for the treatment of cutaneous SCC.
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spelling pubmed-34821822012-10-29 Autophagy Inhibitor Chloroquine Enhanced the Cell Death Inducing Effect of the Flavonoid Luteolin in Metastatic Squamous Cell Carcinoma Cells Verschooten, Lien Barrette, Kathleen Van Kelst, Sofie Rubio Romero, Noemí Proby, Charlotte De Vos, Rita Agostinis, Patrizia Garmyn, Marjan PLoS One Research Article BACKGROUND: Flavonoids are widely proposed as very interesting compounds with possible chemopreventive and therapeutic capacities. METHODS & RESULTS: In this study, we showed that in vitro treatment with the flavonoid Luteolin induced caspase-dependent cell death in a model of human cutaneous squamous cell carcinoma (SCC) derived cells, representing a matched pair of primary tumor and its metastasis. Notably, no cytotoxic effects were observed in normal human keratinocytes when treated with similar doses of Luteolin. Luteolin-induced apoptosis was accompanied by inhibition of AKT signaling, and sensitivity decreased with tumor progression, as the primary MET1 SCC cells were considerably more sensitive to Luteolin than the isogenic metastatic MET4 cells. Extensive intracellular vacuolization was observed in Luteolin-treated MET4 cells, which were characterized as acidic lysosomal vacuoles, suggesting the involvement of autophagy. Transmission electron microscopy, mRFP-GFP-LC3 assay and p62 protein degradation, confirmed that Luteolin stimulated the autophagic process in the metastatic MET4 cells. Blocking autophagy using chloroquine magnified Luteolin-induced apoptosis in the metastatic SCC cells. CONCLUSION: Together, these results suggest that Luteolin has the capacity to induce selectively apoptotic cell death both in primary cutaneous SCC cells and in metastatic SCC cells in combination with chloroquine, an inhibitor of autophagosomal degradation. Hence, Luteolin might be a promising agent for the treatment of cutaneous SCC. Public Library of Science 2012-10-26 /pmc/articles/PMC3482182/ /pubmed/23110223 http://dx.doi.org/10.1371/journal.pone.0048264 Text en © 2012 Verschooten et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Verschooten, Lien
Barrette, Kathleen
Van Kelst, Sofie
Rubio Romero, Noemí
Proby, Charlotte
De Vos, Rita
Agostinis, Patrizia
Garmyn, Marjan
Autophagy Inhibitor Chloroquine Enhanced the Cell Death Inducing Effect of the Flavonoid Luteolin in Metastatic Squamous Cell Carcinoma Cells
title Autophagy Inhibitor Chloroquine Enhanced the Cell Death Inducing Effect of the Flavonoid Luteolin in Metastatic Squamous Cell Carcinoma Cells
title_full Autophagy Inhibitor Chloroquine Enhanced the Cell Death Inducing Effect of the Flavonoid Luteolin in Metastatic Squamous Cell Carcinoma Cells
title_fullStr Autophagy Inhibitor Chloroquine Enhanced the Cell Death Inducing Effect of the Flavonoid Luteolin in Metastatic Squamous Cell Carcinoma Cells
title_full_unstemmed Autophagy Inhibitor Chloroquine Enhanced the Cell Death Inducing Effect of the Flavonoid Luteolin in Metastatic Squamous Cell Carcinoma Cells
title_short Autophagy Inhibitor Chloroquine Enhanced the Cell Death Inducing Effect of the Flavonoid Luteolin in Metastatic Squamous Cell Carcinoma Cells
title_sort autophagy inhibitor chloroquine enhanced the cell death inducing effect of the flavonoid luteolin in metastatic squamous cell carcinoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482182/
https://www.ncbi.nlm.nih.gov/pubmed/23110223
http://dx.doi.org/10.1371/journal.pone.0048264
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