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Comparative Gene Expression Analysis in WM164 Melanoma Cells Revealed That β-β-Dimethylacrylshikonin Leads to ROS Generation, Loss of Mitochondrial Membrane Potential, and Autophagy Induction

Skin cancer is currently diagnosed as one in every three cancers. Melanoma, the most aggressive form of skin cancer, is responsible for 79% of skin cancer deaths and the incidence is rising faster than in any other solid tumor type. Previously, we have demonstrated that dimethylacrylshikonin (DMAS),...

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Autores principales: Kretschmer, Nadine, Deutsch, Alexander, Durchschein, Christin, Rinner, Beate, Stallinger, Alexander, Higareda-Almaraz, Juan Carlos, Scheideler, Marcel, Lohberger, Birgit, Bauer, Rudolf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278572/
https://www.ncbi.nlm.nih.gov/pubmed/30380804
http://dx.doi.org/10.3390/molecules23112823
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author Kretschmer, Nadine
Deutsch, Alexander
Durchschein, Christin
Rinner, Beate
Stallinger, Alexander
Higareda-Almaraz, Juan Carlos
Scheideler, Marcel
Lohberger, Birgit
Bauer, Rudolf
author_facet Kretschmer, Nadine
Deutsch, Alexander
Durchschein, Christin
Rinner, Beate
Stallinger, Alexander
Higareda-Almaraz, Juan Carlos
Scheideler, Marcel
Lohberger, Birgit
Bauer, Rudolf
author_sort Kretschmer, Nadine
collection PubMed
description Skin cancer is currently diagnosed as one in every three cancers. Melanoma, the most aggressive form of skin cancer, is responsible for 79% of skin cancer deaths and the incidence is rising faster than in any other solid tumor type. Previously, we have demonstrated that dimethylacrylshikonin (DMAS), isolated from the roots of Onosma paniculata (Boraginaceae), exhibited the lowest IC(50) values against different tumor types out of several isolated shikonin derivatives. DMAS was especially cytotoxic towards melanoma cells and led to apoptosis and cell cycle arrest. In this study, we performed a comprehensive gene expression study to investigate the mechanism of action in more detail. Gene expression signature was compared to vehicle-treated WM164 control cells after 24 h of DMAS treatment; where 1192 distinct mRNAs could be identified as expressed in all replicates and 89 were at least 2-fold differentially expressed. DMAS favored catabolic processes and led in particular to p62 increase which is involved in cell growth, survival, and autophagy. More in-depth experiments revealed that DMAS led to autophagy, ROS generation, and loss of mitochondrial membrane potential in different melanoma cells. It has been reported that the induction of an autophagic cell death represents a highly effective approach in melanoma therapy.
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spelling pubmed-62785722018-12-13 Comparative Gene Expression Analysis in WM164 Melanoma Cells Revealed That β-β-Dimethylacrylshikonin Leads to ROS Generation, Loss of Mitochondrial Membrane Potential, and Autophagy Induction Kretschmer, Nadine Deutsch, Alexander Durchschein, Christin Rinner, Beate Stallinger, Alexander Higareda-Almaraz, Juan Carlos Scheideler, Marcel Lohberger, Birgit Bauer, Rudolf Molecules Article Skin cancer is currently diagnosed as one in every three cancers. Melanoma, the most aggressive form of skin cancer, is responsible for 79% of skin cancer deaths and the incidence is rising faster than in any other solid tumor type. Previously, we have demonstrated that dimethylacrylshikonin (DMAS), isolated from the roots of Onosma paniculata (Boraginaceae), exhibited the lowest IC(50) values against different tumor types out of several isolated shikonin derivatives. DMAS was especially cytotoxic towards melanoma cells and led to apoptosis and cell cycle arrest. In this study, we performed a comprehensive gene expression study to investigate the mechanism of action in more detail. Gene expression signature was compared to vehicle-treated WM164 control cells after 24 h of DMAS treatment; where 1192 distinct mRNAs could be identified as expressed in all replicates and 89 were at least 2-fold differentially expressed. DMAS favored catabolic processes and led in particular to p62 increase which is involved in cell growth, survival, and autophagy. More in-depth experiments revealed that DMAS led to autophagy, ROS generation, and loss of mitochondrial membrane potential in different melanoma cells. It has been reported that the induction of an autophagic cell death represents a highly effective approach in melanoma therapy. MDPI 2018-10-30 /pmc/articles/PMC6278572/ /pubmed/30380804 http://dx.doi.org/10.3390/molecules23112823 Text en © 2018 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
Kretschmer, Nadine
Deutsch, Alexander
Durchschein, Christin
Rinner, Beate
Stallinger, Alexander
Higareda-Almaraz, Juan Carlos
Scheideler, Marcel
Lohberger, Birgit
Bauer, Rudolf
Comparative Gene Expression Analysis in WM164 Melanoma Cells Revealed That β-β-Dimethylacrylshikonin Leads to ROS Generation, Loss of Mitochondrial Membrane Potential, and Autophagy Induction
title Comparative Gene Expression Analysis in WM164 Melanoma Cells Revealed That β-β-Dimethylacrylshikonin Leads to ROS Generation, Loss of Mitochondrial Membrane Potential, and Autophagy Induction
title_full Comparative Gene Expression Analysis in WM164 Melanoma Cells Revealed That β-β-Dimethylacrylshikonin Leads to ROS Generation, Loss of Mitochondrial Membrane Potential, and Autophagy Induction
title_fullStr Comparative Gene Expression Analysis in WM164 Melanoma Cells Revealed That β-β-Dimethylacrylshikonin Leads to ROS Generation, Loss of Mitochondrial Membrane Potential, and Autophagy Induction
title_full_unstemmed Comparative Gene Expression Analysis in WM164 Melanoma Cells Revealed That β-β-Dimethylacrylshikonin Leads to ROS Generation, Loss of Mitochondrial Membrane Potential, and Autophagy Induction
title_short Comparative Gene Expression Analysis in WM164 Melanoma Cells Revealed That β-β-Dimethylacrylshikonin Leads to ROS Generation, Loss of Mitochondrial Membrane Potential, and Autophagy Induction
title_sort comparative gene expression analysis in wm164 melanoma cells revealed that β-β-dimethylacrylshikonin leads to ros generation, loss of mitochondrial membrane potential, and autophagy induction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278572/
https://www.ncbi.nlm.nih.gov/pubmed/30380804
http://dx.doi.org/10.3390/molecules23112823
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