title: Hypericin-PDT-induced rapid necrotic death in human squamous cell carcinoma cultures after multiple treatment.
abstract: PDT (photodynamic therapy) has been used for the treatment of NMCC (non-melanoma cutaneous cancer) particularly, human SCC (squamous cell carcinoma). However, the nature of the photosensitizer, the activation light source and the mode of cell death induced post-PDT remains elusive. We tried to optimize PDT using the light-activated (320-400 nm) St John's Wort-derived compound, Hyp (hypericin). The work highlights the potential mode of cell death and the increased efficacy of the technique associated with multiple Hyp-PDT treatment. SCC cells were exposed to different concentrations of Hyp and activated with light at 1 J/cm2 for 1 or 2 days. Thereafter with the optimum dose of Hyp proliferation, ROS (reactive oxygen species), and apoptosis were analysed by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay, FACS analysis and Fluorescent/Phase contrast microscopy was carried out for morphological studies. Hyp-PDT produces more ROS after 1 day compared with 2 days and the mode of cell death is a necrotic caspase-independent mechanism. We propose a novel 'double-hit/2-day' strategy to reduce the viability in SCC using Hyp-based PDT as an adjunctive treatment modality.
authors.affiliation: Department of Human Biology, University of Cape Town, Cape Town, South Africa.
authors.forename: Krishna V
authors.initials: KV
authors.lastname: Sharma
authors.forename: Lester M
authors.initials: LM
authors.lastname: Davids
mesh_terms: D000873:Anthracenes; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D020902:Hypericum / Q000737:chemistry; D009336:Necrosis / Q000188:drug therapy*; D010569:Perylene / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010778:Photochemotherapy / Q000379:methods*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000873:Anthracenes; D017382:Reactive Oxygen Species; D010569:Perylene; C004965:hypericin