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...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5602 |
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| author | Thais P. Pivetta Tânia Vieira Jorge C. Silva Paulo A. Ribeiro Maria Raposo |
| author_facet | Thais P. Pivetta Tânia Vieira Jorge C. Silva Paulo A. Ribeiro Maria Raposo |
| author_sort | Thais P. Pivetta |
| collection | DOAJ |
| 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<sub>50</sub> 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<sub>50</sub> 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<sub>50</sub> 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. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:26:13Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-8c7daaa1ccfc4eb6b19c56521495c7d32023-11-17T11:36:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246560210.3390/ijms24065602Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro ScreeningThais P. Pivetta0Tânia Vieira1Jorge C. Silva2Paulo A. Ribeiro3Maria Raposo4CEFITEC, Department of Physics, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, PortugalCENIMAT/I3N, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, PortugalCENIMAT/I3N, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, PortugalLaboratory for Instrumentation, Biomedical Engineering and Radiation Physics (LIBPhys-UNL), Department of Physics, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, PortugalLaboratory for Instrumentation, Biomedical Engineering and Radiation Physics (LIBPhys-UNL), Department of Physics, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, PortugalPhotodynamic 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<sub>50</sub> 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<sub>50</sub> 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<sub>50</sub> 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.https://www.mdpi.com/1422-0067/24/6/5602photodynamic therapyphotosensitizerskin cancerreactive oxygen species |
| spellingShingle | Thais P. Pivetta Tânia Vieira Jorge C. Silva Paulo A. Ribeiro Maria Raposo Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening International Journal of Molecular Sciences photodynamic therapy photosensitizer skin cancer reactive oxygen species |
| 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 | photodynamic therapy photosensitizer skin cancer reactive oxygen species |
| url | https://www.mdpi.com/1422-0067/24/6/5602 |
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