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• W2000452932 abstract "Objective Head and neck squamous cell carcinoma (HNSCC) is the eighth most common malignancy worldwide. However, treatment options are still limited. With the aim to improve the survival rate, tissue preservation and quality-of-life issues, photodynamic therapy (PDT) was recently introduced. This treatment regime is based on the uptake of a fluorescent photosensitizer into cancer cells. Following light activation of the photosensitizer, highly toxic metabolites are generated that may cause cell death. In this in-vitro study we explored the effects of two photosensitizers alone, and in combination in HNSCC. Material and methods HNSCC cells (UMB-SCC 745) were cultivated under standard conditions and incubated with hypericin (Invitrogen, Basel, Switzerland) or the meso-tetrahydroxyphenylchlorin derivative Foslipos (Biolitec, Jena, Germany) in concentrations ranging from 10 to 0.6 μg/ml for 0–24 h. In addition, a combination of hypericin and Foslipos was used (final concentration 20–1.25 μg/ml). The cells were then washed, illuminated with 5 J/cm 2 for 15 min and further cultivated for 0–24 h. A dark toxicity assay was performed for each photosensitizer using a BrdU proliferation assay (Roche, Basel, Switzerland). The uptake kinetics of the photosensitizers were investigated by ELISA fluorescence measurements at 540±40 nm and by confocal microscopy. Furthermore, PDT effects were monitored by live cell imaging and MTT viability tests. Intracellular photosensitizer localization was monitored by confocal microscopy together with organelle stains. Results Dark toxicity assays showed that photosensitizer concentrations of 10 μg/ml are cytotoxic, while concentrations of 2.5 μg/ml were well tolerated. Photosensitizers accumulated over time in the cytoplasm of HNSCC cells, already reaching the maximum after 5 h. Confocal analyses indicated that photosensitizers are located at cell membranes, including the cytoplasmic and the nuclear membrane. Live cell-imaging studies showed that single applications of either hypericin or Foslipos (each 2.5 μg/ml) resulted in death of near to 100% of HNSCC cells within 12 h. After treatment with a mixture of both photosensitizers (total concentration 2.5 μg/ml) all HNSCC cells had already been killed after 3 h. Conclusion Our data indicate that the photosensitizers hypericin and Foslipos may have synergistic phototoxic effects on HNSCC cells in vitro . We hypothesize that this effect may be the result of the hypericin emission spectrum exciting Foslipos. The application of mixtures with overall lower concentrations of each photosensitizer may be advantageous compared to established conditions." @default.
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• W2000452932 date "2009-05-01" @default.
• W2000452932 modified "2023-09-26" @default.
• W2000452932 title "[5.05] Photodynamic effects of hypericin and Foslipos in head and neck squamous cell carcinoma in vitro" @default.
• W2000452932 doi "https://doi.org/10.1016/j.mla.2009.02.033" @default.
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