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Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening
Photodynamic therapy is a minimally invasive procedure used in the treatment of several diseases, including some types of cancer. It is based on photosensitizer molecules, which, in the presence of oxygen and light, lead to the formation of reactive oxygen species (ROS) and consequent cell death. Th...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10054552/ https://www.ncbi.nlm.nih.gov/pubmed/36982675 http://dx.doi.org/10.3390/ijms24065602 |
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author | Pivetta, Thais P. Vieira, Tânia Silva, Jorge C. Ribeiro, Paulo A. Raposo, Maria |
author_facet | Pivetta, Thais P. Vieira, Tânia Silva, Jorge C. Ribeiro, Paulo A. Raposo, Maria |
author_sort | Pivetta, Thais P. |
collection | PubMed |
description | Photodynamic therapy is a minimally invasive procedure used in the treatment of several diseases, including some types of cancer. It is based on photosensitizer molecules, which, in the presence of oxygen and light, lead to the formation of reactive oxygen species (ROS) and consequent cell death. The selection of the photosensitizer molecule is important for the therapy efficiency; therefore, many molecules such as dyes, natural products and metallic complexes have been investigated regarding their photosensitizing potential. In this work, the phototoxic potential of the DNA-intercalating molecules—the dyes methylene blue (MB), acridine orange (AO) and gentian violet (GV); the natural products curcumin (CUR), quercetin (QT) and epigallocatechin gallate (EGCG); and the chelating compounds neocuproine (NEO), 1,10-phenanthroline (PHE) and 2,2′-bipyridyl (BIPY)—were analyzed. The cytotoxicity of these chemicals was tested in vitro in non-cancer keratinocytes (HaCaT) and squamous cell carcinoma (MET1) cell lines. A phototoxicity assay and the detection of intracellular ROS were performed in MET1 cells. Results revealed that the IC(50) values of the dyes and curcumin in MET1 cells were lower than 30 µM, while the values for the natural products QT and EGCG and the chelating agents BIPY and PHE were higher than 100 µM. The IC(50) of MB and AO was greatly affected by irradiation when submitted to 640 nm and 457 nm light sources, respectively. ROS detection was more evident for cells treated with AO at low concentrations. In studies with the melanoma cell line WM983b, cells were more resistant to MB and AO and presented slightly higher IC(50) values, in line with the results of the phototoxicity assays. This study reveals that many molecules can act as photosensitizers, but the effect depends on the cell line and the concentration of the chemical. Finally, significant photosensitizing activity of acridine orange at low concentrations and moderate light doses was demonstrated. |
format | Online Article Text |
id | pubmed-10054552 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100545522023-03-30 Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening Pivetta, Thais P. Vieira, Tânia Silva, Jorge C. Ribeiro, Paulo A. Raposo, Maria Int J Mol Sci Article Photodynamic therapy is a minimally invasive procedure used in the treatment of several diseases, including some types of cancer. It is based on photosensitizer molecules, which, in the presence of oxygen and light, lead to the formation of reactive oxygen species (ROS) and consequent cell death. The selection of the photosensitizer molecule is important for the therapy efficiency; therefore, many molecules such as dyes, natural products and metallic complexes have been investigated regarding their photosensitizing potential. In this work, the phototoxic potential of the DNA-intercalating molecules—the dyes methylene blue (MB), acridine orange (AO) and gentian violet (GV); the natural products curcumin (CUR), quercetin (QT) and epigallocatechin gallate (EGCG); and the chelating compounds neocuproine (NEO), 1,10-phenanthroline (PHE) and 2,2′-bipyridyl (BIPY)—were analyzed. The cytotoxicity of these chemicals was tested in vitro in non-cancer keratinocytes (HaCaT) and squamous cell carcinoma (MET1) cell lines. A phototoxicity assay and the detection of intracellular ROS were performed in MET1 cells. Results revealed that the IC(50) values of the dyes and curcumin in MET1 cells were lower than 30 µM, while the values for the natural products QT and EGCG and the chelating agents BIPY and PHE were higher than 100 µM. The IC(50) of MB and AO was greatly affected by irradiation when submitted to 640 nm and 457 nm light sources, respectively. ROS detection was more evident for cells treated with AO at low concentrations. In studies with the melanoma cell line WM983b, cells were more resistant to MB and AO and presented slightly higher IC(50) values, in line with the results of the phototoxicity assays. This study reveals that many molecules can act as photosensitizers, but the effect depends on the cell line and the concentration of the chemical. Finally, significant photosensitizing activity of acridine orange at low concentrations and moderate light doses was demonstrated. MDPI 2023-03-15 /pmc/articles/PMC10054552/ /pubmed/36982675 http://dx.doi.org/10.3390/ijms24065602 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Pivetta, Thais P. Vieira, Tânia Silva, Jorge C. Ribeiro, Paulo A. Raposo, Maria Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening |
title | Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening |
title_full | Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening |
title_fullStr | Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening |
title_full_unstemmed | Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening |
title_short | Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening |
title_sort | phototoxic potential of different dna intercalators for skin cancer therapy: in vitro screening |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10054552/ https://www.ncbi.nlm.nih.gov/pubmed/36982675 http://dx.doi.org/10.3390/ijms24065602 |
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