Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Pivetta, Thais P., Vieira, Tânia, Silva, Jorge C., Ribeiro, Paulo A., Raposo, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785015698477547520
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
work_keys_str_mv AT pivettathaisp phototoxicpotentialofdifferentdnaintercalatorsforskincancertherapyinvitroscreening
AT vieiratania phototoxicpotentialofdifferentdnaintercalatorsforskincancertherapyinvitroscreening
AT silvajorgec phototoxicpotentialofdifferentdnaintercalatorsforskincancertherapyinvitroscreening
AT ribeiropauloa phototoxicpotentialofdifferentdnaintercalatorsforskincancertherapyinvitroscreening
AT raposomaria phototoxicpotentialofdifferentdnaintercalatorsforskincancertherapyinvitroscreening