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Alectinib treatment improves photodynamic therapy in cancer cell lines of different origin

BACKGROUND: Photodynamic therapy with a photosensitizer such as protoporphyrin-IX, a light sensitive metabolite of heme synthesis, is a highly selective treatment for various carcinomas. In previous studies, we found a significant down regulation of the relevant enzyme ferrochelatase in gastrointest...

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Autores principales: Gillissen, Bernhard, Richter, Antje, Essmann, Frank, Kemmner, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404354/
https://www.ncbi.nlm.nih.gov/pubmed/34461853
http://dx.doi.org/10.1186/s12885-021-08667-x
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author Gillissen, Bernhard
Richter, Antje
Essmann, Frank
Kemmner, Wolfgang
author_facet Gillissen, Bernhard
Richter, Antje
Essmann, Frank
Kemmner, Wolfgang
author_sort Gillissen, Bernhard
collection PubMed
description BACKGROUND: Photodynamic therapy with a photosensitizer such as protoporphyrin-IX, a light sensitive metabolite of heme synthesis, is a highly selective treatment for various carcinomas. In previous studies, we found a significant down regulation of the relevant enzyme ferrochelatase in gastrointestinal carcinomas leading to an accumulation of protoporphyrin-IX within the tumor cells. Recent studies showed that a novel anti-cancer drug, Alectinib, an orally available, highly selective, potent second-generation inhibitor of anaplastic lymphoma tyrosinkinase binds to ferrochelatase. Therefore, we were interested to see whether Alectinib treatment might lead to an accumulation of protoporphyrin IX. METHODS: Tumor cells of different origin were cultured, treated with LED-light and Alectinib. Results were gained by flow cytometry, immunohistochemistry and western blotting. Apoptosis was determined by flow cytometric analysis of Annexin V-FITC stained cells. In addition, cells were counterstained with propidium iodide to distinguish early apoptotic cells and late apoptotic/necrotic cells. RESULTS: Here, we report that photodynamic treatment of tumor cell lines of different origin in combination with Alectinib increased protoporphyrin-IX specific fluorescence and concomitantly cell death. CONCLUSIONS: The usage of Alectinib could be another step for enhancing the effectiveness of photodynamic therapy. Further experiments will show whether photodynamic therapy in combination with Alectinib could be a new strategy for the treatment of e.g. peritoneal disseminated carcinomas. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08667-x.
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spelling pubmed-84043542021-08-31 Alectinib treatment improves photodynamic therapy in cancer cell lines of different origin Gillissen, Bernhard Richter, Antje Essmann, Frank Kemmner, Wolfgang BMC Cancer Research Article BACKGROUND: Photodynamic therapy with a photosensitizer such as protoporphyrin-IX, a light sensitive metabolite of heme synthesis, is a highly selective treatment for various carcinomas. In previous studies, we found a significant down regulation of the relevant enzyme ferrochelatase in gastrointestinal carcinomas leading to an accumulation of protoporphyrin-IX within the tumor cells. Recent studies showed that a novel anti-cancer drug, Alectinib, an orally available, highly selective, potent second-generation inhibitor of anaplastic lymphoma tyrosinkinase binds to ferrochelatase. Therefore, we were interested to see whether Alectinib treatment might lead to an accumulation of protoporphyrin IX. METHODS: Tumor cells of different origin were cultured, treated with LED-light and Alectinib. Results were gained by flow cytometry, immunohistochemistry and western blotting. Apoptosis was determined by flow cytometric analysis of Annexin V-FITC stained cells. In addition, cells were counterstained with propidium iodide to distinguish early apoptotic cells and late apoptotic/necrotic cells. RESULTS: Here, we report that photodynamic treatment of tumor cell lines of different origin in combination with Alectinib increased protoporphyrin-IX specific fluorescence and concomitantly cell death. CONCLUSIONS: The usage of Alectinib could be another step for enhancing the effectiveness of photodynamic therapy. Further experiments will show whether photodynamic therapy in combination with Alectinib could be a new strategy for the treatment of e.g. peritoneal disseminated carcinomas. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08667-x. BioMed Central 2021-08-30 /pmc/articles/PMC8404354/ /pubmed/34461853 http://dx.doi.org/10.1186/s12885-021-08667-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Gillissen, Bernhard
Richter, Antje
Essmann, Frank
Kemmner, Wolfgang
Alectinib treatment improves photodynamic therapy in cancer cell lines of different origin
title Alectinib treatment improves photodynamic therapy in cancer cell lines of different origin
title_full Alectinib treatment improves photodynamic therapy in cancer cell lines of different origin
title_fullStr Alectinib treatment improves photodynamic therapy in cancer cell lines of different origin
title_full_unstemmed Alectinib treatment improves photodynamic therapy in cancer cell lines of different origin
title_short Alectinib treatment improves photodynamic therapy in cancer cell lines of different origin
title_sort alectinib treatment improves photodynamic therapy in cancer cell lines of different origin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404354/
https://www.ncbi.nlm.nih.gov/pubmed/34461853
http://dx.doi.org/10.1186/s12885-021-08667-x
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