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Verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity

Verteporfin (VP) was first used in Photodynamic therapy, where a non-thermal laser light (689 nm) in the presence of oxygen activates the drug to produce highly reactive oxygen radicals, resulting in local cell and tissue damage. However, it has also been shown that Verteporfin can have non-photoact...

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Autores principales: Konstantinou, Eleni K., Notomi, Shoji, Kosmidou, Cassandra, Brodowska, Katarzyna, Al-Moujahed, Ahmad, Nicolaou, Fotini, Tsoka, Pavlina, Gragoudas, Evangelos, Miller, Joan W., Young, Lucy H., Vavvas, Demetrios G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399488/
https://www.ncbi.nlm.nih.gov/pubmed/28429726
http://dx.doi.org/10.1038/srep46581
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author Konstantinou, Eleni K.
Notomi, Shoji
Kosmidou, Cassandra
Brodowska, Katarzyna
Al-Moujahed, Ahmad
Nicolaou, Fotini
Tsoka, Pavlina
Gragoudas, Evangelos
Miller, Joan W.
Young, Lucy H.
Vavvas, Demetrios G.
author_facet Konstantinou, Eleni K.
Notomi, Shoji
Kosmidou, Cassandra
Brodowska, Katarzyna
Al-Moujahed, Ahmad
Nicolaou, Fotini
Tsoka, Pavlina
Gragoudas, Evangelos
Miller, Joan W.
Young, Lucy H.
Vavvas, Demetrios G.
author_sort Konstantinou, Eleni K.
collection PubMed
description Verteporfin (VP) was first used in Photodynamic therapy, where a non-thermal laser light (689 nm) in the presence of oxygen activates the drug to produce highly reactive oxygen radicals, resulting in local cell and tissue damage. However, it has also been shown that Verteporfin can have non-photoactivated effects such as interference with the YAP-TEAD complex of the HIPPO pathway, resulting in growth inhibition of several neoplasias. More recently, it was proposed that, another non-light mediated effect of VP is the formation of cross-linked oligomers and high molecular weight protein complexes (HMWC) that are hypothesized to interfere with autophagy and cell growth. Here, in a series of experiments, using human uveal melanoma cells (MEL 270), human embryonic kidney cells (HEK) and breast cancer cells (MCF7) we showed that Verteporfin-induced HMWC require the presence of light. Furthermore, we showed that the mechanism of this cross-linking, which involves both singlet oxygen and radical generation, can occur very efficiently even after lysis of the cells, if the lysate is not protected from ambient light. This work offers a better understanding regarding VP’s mechanisms of action and suggests caution when one studies the non-light mediated actions of this drug.
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spelling pubmed-53994882017-04-24 Verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity Konstantinou, Eleni K. Notomi, Shoji Kosmidou, Cassandra Brodowska, Katarzyna Al-Moujahed, Ahmad Nicolaou, Fotini Tsoka, Pavlina Gragoudas, Evangelos Miller, Joan W. Young, Lucy H. Vavvas, Demetrios G. Sci Rep Article Verteporfin (VP) was first used in Photodynamic therapy, where a non-thermal laser light (689 nm) in the presence of oxygen activates the drug to produce highly reactive oxygen radicals, resulting in local cell and tissue damage. However, it has also been shown that Verteporfin can have non-photoactivated effects such as interference with the YAP-TEAD complex of the HIPPO pathway, resulting in growth inhibition of several neoplasias. More recently, it was proposed that, another non-light mediated effect of VP is the formation of cross-linked oligomers and high molecular weight protein complexes (HMWC) that are hypothesized to interfere with autophagy and cell growth. Here, in a series of experiments, using human uveal melanoma cells (MEL 270), human embryonic kidney cells (HEK) and breast cancer cells (MCF7) we showed that Verteporfin-induced HMWC require the presence of light. Furthermore, we showed that the mechanism of this cross-linking, which involves both singlet oxygen and radical generation, can occur very efficiently even after lysis of the cells, if the lysate is not protected from ambient light. This work offers a better understanding regarding VP’s mechanisms of action and suggests caution when one studies the non-light mediated actions of this drug. Nature Publishing Group 2017-04-21 /pmc/articles/PMC5399488/ /pubmed/28429726 http://dx.doi.org/10.1038/srep46581 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Konstantinou, Eleni K.
Notomi, Shoji
Kosmidou, Cassandra
Brodowska, Katarzyna
Al-Moujahed, Ahmad
Nicolaou, Fotini
Tsoka, Pavlina
Gragoudas, Evangelos
Miller, Joan W.
Young, Lucy H.
Vavvas, Demetrios G.
Verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity
title Verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity
title_full Verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity
title_fullStr Verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity
title_full_unstemmed Verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity
title_short Verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity
title_sort verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399488/
https://www.ncbi.nlm.nih.gov/pubmed/28429726
http://dx.doi.org/10.1038/srep46581
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