Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening
Thais P Pivetta1,2, Tânia Vieira3, Jorge C Silva3
1CEFITEC, Department of Physics, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal.
Abstract:
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 IC50 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 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.
Insights
Acridine orange shows significant photosensitizing activity for photodynamic therapy, particularly at low concentrations and moderate light doses. Its effectiveness varies by cell line and chemical concentration, highlighting the importance of careful selection for cancer treatment.
Area of Science:
- Photodynamic therapy (PDT) research
- Photochemistry and photobiology
- Cancer treatment modalities
Background:
- Photodynamic therapy utilizes photosensitizers, oxygen, and light to generate reactive oxygen species (ROS) for cell death, applicable in cancer treatment.
- Selecting effective photosensitizers is crucial for PDT efficacy, prompting investigation into various molecular classes including dyes, natural products, and metal complexes.
Purpose of the Study:
- To evaluate the phototoxic potential of various DNA-intercalating molecules as photosensitizers for photodynamic therapy.
- To compare the cytotoxicity and phototoxicity of selected dyes, natural products, and chelating agents across different cell lines.
Main Methods:
- In vitro cytotoxicity assays (IC50 determination) on HaCaT and MET1 cell lines.
- Phototoxicity assays and intracellular reactive oxygen species (ROS) detection in MET1 cells.
- Evaluation of photosensitizing potential of methylene blue (MB), acridine orange (AO), gentian violet (GV), curcumin (CUR), quercetin (QT), epigallocatechin gallate (EGCG), neocuproine (NEO), 1,10-phenanthroline (PHE), and 2,2'-bipyridyl (BIPY).
Main Results:
- Dyes and curcumin exhibited lower IC50 values (<30 µM) in MET1 cells compared to QT, EGCG, BIPY, and PHE (>100 µM).
- Methylene blue and acridine orange IC50 values were significantly affected by irradiation at 640 nm and 457 nm, respectively.
- Acridine orange demonstrated more evident ROS production at low concentrations, and significant photosensitizing activity was observed at low concentrations and moderate light doses.
Conclusions:
- Many investigated molecules possess photosensitizing capabilities, but their efficacy is dependent on the specific cell line and the concentration used.
- Acridine orange shows promising significant photosensitizing activity for potential use in photodynamic therapy, especially under optimized conditions.
- The study underscores the need for careful selection of photosensitizers and conditions for effective photodynamic therapy applications.
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