PMID- 36982675 OWN - NLM STAT- MEDLINE DCOM- 20230330 LR - 20230331 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 6 DP - 2023 Mar 15 TI - Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening. LID - 10.3390/ijms24065602 [doi] LID - 5602 AB - 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 microM, while the values for the natural products QT and EGCG and the chelating agents BIPY and PHE were higher than 100 microM. 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. FAU - Pivetta, Thais P AU - Pivetta TP AUID- ORCID: 0000-0003-4801-3655 AD - CEFITEC, Department of Physics, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal. AD - 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. FAU - Vieira, Tania AU - Vieira T AD - CENIMAT/I3N, Departamento de Fisica, Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. FAU - Silva, Jorge C AU - Silva JC AUID- ORCID: 0000-0001-9959-4272 AD - CENIMAT/I3N, Departamento de Fisica, Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. FAU - Ribeiro, Paulo A AU - Ribeiro PA AUID- ORCID: 0000-0001-9665-7610 AD - 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. FAU - Raposo, Maria AU - Raposo M AUID- ORCID: 0000-0003-4710-0693 AD - 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. LA - eng GR - PD/00193/2012/Fundacao para a Ciencia e Tecnologia/ GR - UIDB/04378/2020/Fundacao para a Ciencia e Tecnologia/ GR - UIDB/00068/2020/Fundacao para a Ciencia e Tecnologia/ GR - UIDB/04559/2020/Fundacao para a Ciencia e Tecnologia/ GR - UIDP/04559/2020/Fundacao para a Ciencia e Tecnologia/ GR - UIDB/50025/2020/Fundacao para a Ciencia e Tecnologia/ PT - Journal Article DEP - 20230315 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Photosensitizing Agents) RN - 0 (Intercalating Agents) RN - 0 (Reactive Oxygen Species) RN - IT942ZTH98 (Curcumin) RN - F30N4O6XVV (Acridine Orange) RN - 0 (Coloring Agents) SB - IM MH - Humans MH - Photosensitizing Agents/chemistry MH - Intercalating Agents/pharmacology MH - Reactive Oxygen Species/metabolism MH - *Curcumin/pharmacology MH - Acridine Orange MH - Cell Line, Tumor MH - Early Detection of Cancer MH - *Photochemotherapy/methods MH - *Skin Neoplasms/drug therapy/metabolism MH - *Dermatitis, Phototoxic/drug therapy MH - Coloring Agents PMC - PMC10054552 OTO - NOTNLM OT - photodynamic therapy OT - photosensitizer OT - reactive oxygen species OT - skin cancer COIS- The authors declare no conflict of interest. EDAT- 2023/03/30 06:00 MHDA- 2023/03/30 06:11 PMCR- 2023/03/15 CRDT- 2023/03/29 01:38 PHST- 2023/01/21 00:00 [received] PHST- 2023/03/03 00:00 [revised] PHST- 2023/03/11 00:00 [accepted] PHST- 2023/03/30 06:11 [medline] PHST- 2023/03/29 01:38 [entrez] PHST- 2023/03/30 06:00 [pubmed] PHST- 2023/03/15 00:00 [pmc-release] AID - ijms24065602 [pii] AID - ijms-24-05602 [pii] AID - 10.3390/ijms24065602 [doi] PST - epublish SO - Int J Mol Sci. 2023 Mar 15;24(6):5602. doi: 10.3390/ijms24065602.