title: Photodynamic mechanisms induced by a combination of hypericin and a chlorin based-photosensitizer in head and neck squamous cell carcinoma cells.
abstract: The aim of this study was to elucidate photodynamic therapy (PDT) effects mediated by hypericin and a liposomal meso-tetrahydroxyphenyl chlorin (mTHPC) derivative, with focus on their 1:1 mixture, on head and neck squamous cell carcinoma cell lines. Absorption, excitation and photobleaching were monitored using fluorescence spectrometry, showing the same spectral patterns for the mixture as measured for single photosensitizers. In the mixture mTHPC showed a prolonged photo-stability. Singlet oxygen yield for light-activated mTHPC was Φ(Δ) = 0.66, for hypericin Φ(Δ) = 0.25 and for the mixture Φ(Δ) = ~0.4. A linear increase of singlet oxygen yield for mTHPC and the mixture was found, whereas hypericin achieved saturation after 35 min. Reactive oxygen species fluorescence was only visible after hypericin and mixture-induced PDT. Cell viability was also more affected with these two treatment options under the selected conditions. Examination of death pathways showed that hypericin-mediated cell death was apoptotic, with mTHPC necrotic and the 1:1 mixture showed features of both. Changes in gene expression after PDT indicated strong up-regulation of selected heat-shock proteins. The application of photosensitizer mixtures with the features of reduced dark toxicity and combined apoptotic and necrotic cell death may be beneficial in clinical PDT. This will be the focus of our future investigations.
authors.affiliation: Institute of Anatomy, University of Zurich, Zurich, Switzerland. emina.besicgyenge@uzh.ch
authors.forename: Emina Besic
authors.initials: EB
authors.lastname: Gyenge
authors.forename: Daniel
authors.initials: D
authors.lastname: Lüscher
authors.forename: Patrick
authors.initials: P
authors.lastname: Forny
authors.forename: Martina
authors.initials: M
authors.lastname: Antoniol
authors.forename: Georg
authors.initials: G
authors.lastname: Geisberger
authors.forename: Heinrich
authors.initials: H
authors.lastname: Walt
authors.forename: Greta
authors.initials: G
authors.lastname: Patzke
authors.forename: Caroline
authors.initials: C
authors.lastname: Maake
mesh_terms: D000368:Aged; D000873:Anthracenes; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008027:Light; D008081:Liposomes / Q000737:chemistry; D008297:Male; D008652:Mesoporphyrins / Q000138:chemical synthesis / Q000494:pharmacology*; D008875:Middle Aged; D009336:Necrosis / Q000378:metabolism / Q000473:pathology; D010569:Perylene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D011166:Porphyrins / Q000138:chemical synthesis / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000873:Anthracenes; D006360:Heat-Shock Proteins; D008081:Liposomes; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; C006969:chlorin; D010569:Perylene; C004965:hypericin; C072269:temoporfin