Autophagy inhibitor chloroquine enhanced the cell death inducing effect of the flavonoid luteolin in metastatic squamous cell carcinoma cells.

<h4>Background</h4>Flavonoids are widely proposed as very interesting compounds with possible chemopreventive and therapeutic capacities.<h4>Methods & results</h4>In this study, we showed that in vitro treatment with the flavonoid Luteolin induced caspase-dependent cell d...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lien Verschooten, Kathleen Barrette, Sofie Van Kelst, Noemí Rubio Romero, Charlotte Proby, Rita De Vos, Patrizia Agostinis, Marjan Garmyn
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4679ee69f8044caa930cd58cd5bdd2d0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4679ee69f8044caa930cd58cd5bdd2d0
record_format	dspace
spelling	oai:doaj.org-article:4679ee69f8044caa930cd58cd5bdd2d02021-11-18T08:10:50ZAutophagy inhibitor chloroquine enhanced the cell death inducing effect of the flavonoid luteolin in metastatic squamous cell carcinoma cells.1932-620310.1371/journal.pone.0048264https://doaj.org/article/4679ee69f8044caa930cd58cd5bdd2d02012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23110223/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Flavonoids are widely proposed as very interesting compounds with possible chemopreventive and therapeutic capacities.<h4>Methods & results</h4>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.<h4>Conclusion</h4>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.Lien VerschootenKathleen BarretteSofie Van KelstNoemí Rubio RomeroCharlotte ProbyRita De VosPatrizia AgostinisMarjan GarmynPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e48264 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lien Verschooten Kathleen Barrette Sofie Van Kelst Noemí Rubio Romero Charlotte Proby Rita De Vos Patrizia Agostinis Marjan Garmyn Autophagy inhibitor chloroquine enhanced the cell death inducing effect of the flavonoid luteolin in metastatic squamous cell carcinoma cells.
description	<h4>Background</h4>Flavonoids are widely proposed as very interesting compounds with possible chemopreventive and therapeutic capacities.<h4>Methods & results</h4>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.<h4>Conclusion</h4>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.
format	article
author	Lien Verschooten Kathleen Barrette Sofie Van Kelst Noemí Rubio Romero Charlotte Proby Rita De Vos Patrizia Agostinis Marjan Garmyn
author_facet	Lien Verschooten Kathleen Barrette Sofie Van Kelst Noemí Rubio Romero Charlotte Proby Rita De Vos Patrizia Agostinis Marjan Garmyn
author_sort	Lien Verschooten
title	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_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_sort	autophagy inhibitor chloroquine enhanced the cell death inducing effect of the flavonoid luteolin in metastatic squamous cell carcinoma cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/4679ee69f8044caa930cd58cd5bdd2d0
work_keys_str_mv	AT lienverschooten autophagyinhibitorchloroquineenhancedthecelldeathinducingeffectoftheflavonoidluteolininmetastaticsquamouscellcarcinomacells AT kathleenbarrette autophagyinhibitorchloroquineenhancedthecelldeathinducingeffectoftheflavonoidluteolininmetastaticsquamouscellcarcinomacells AT sofievankelst autophagyinhibitorchloroquineenhancedthecelldeathinducingeffectoftheflavonoidluteolininmetastaticsquamouscellcarcinomacells AT noemirubioromero autophagyinhibitorchloroquineenhancedthecelldeathinducingeffectoftheflavonoidluteolininmetastaticsquamouscellcarcinomacells AT charlotteproby autophagyinhibitorchloroquineenhancedthecelldeathinducingeffectoftheflavonoidluteolininmetastaticsquamouscellcarcinomacells AT ritadevos autophagyinhibitorchloroquineenhancedthecelldeathinducingeffectoftheflavonoidluteolininmetastaticsquamouscellcarcinomacells AT patriziaagostinis autophagyinhibitorchloroquineenhancedthecelldeathinducingeffectoftheflavonoidluteolininmetastaticsquamouscellcarcinomacells AT marjangarmyn autophagyinhibitorchloroquineenhancedthecelldeathinducingeffectoftheflavonoidluteolininmetastaticsquamouscellcarcinomacells
_version_	1718422102707535872

Autophagy inhibitor chloroquine enhanced the cell death inducing effect of the flavonoid luteolin in metastatic squamous cell carcinoma cells.

Ejemplares similares