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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\u2014the 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\u2032-bipyridyl (BIPY)\u2014were 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 IC50 values of the dyes and curcumin in MET1 cells were lower than 30 \u00b5M, while the values for the natural products QT and EGCG and the chelating agents BIPY and PHE were higher than 100 \u00b5M. The IC50 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 IC50 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.<\/jats:p>","DOI":"10.3390\/ijms24065602","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T05:53:44Z","timestamp":1678859624000},"page":"5602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4801-3655","authenticated-orcid":false,"given":"Thais P.","family":"Pivetta","sequence":"first","affiliation":[{"name":"CEFITEC, Department of Physics, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"},{"name":"Laboratory 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, Portugal"}]},{"given":"T\u00e2nia","family":"Vieira","sequence":"additional","affiliation":[{"name":"CENIMAT\/I3N, Departamento de F\u00edsica, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9959-4272","authenticated-orcid":false,"given":"Jorge C.","family":"Silva","sequence":"additional","affiliation":[{"name":"CENIMAT\/I3N, Departamento de F\u00edsica, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9665-7610","authenticated-orcid":false,"given":"Paulo A.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Laboratory 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, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4710-0693","authenticated-orcid":false,"given":"Maria","family":"Raposo","sequence":"additional","affiliation":[{"name":"Laboratory 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, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.pdpdt.2017.06.010","article-title":"Photodynamic Therapy in Dermatology beyond Non-Melanoma Cancer: An Update","volume":"19","author":"Wen","year":"2017","journal-title":"Photodiagnosis Photodyn. 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