Molecular response to hypericin-induced photodamage.
Hypericin (Hyp) is used as a powerful natural photosensitizer in photodynamic therapy (PDT). After selective accumulation in tumor tissue, vessels and matrix, and activated by visible light, it destroys the tumor mainly via generation of reactive oxygen species. After photoactivation, molecular biological mechanisms lead to different cellular endpoints: "biostimulation" (increased proliferation rate), repair of the damage leading to rescue of the cells, autophagy, apoptosis and necrosis. Growth stimulation after low-dose Hyp-PDT seems to be induced via the p38 or JNK survival pathways. Since both pathways are also activated by stress, modification of these pathways may also contribute to rescue mechanisms as well as to damage processing. By increasing PDT doses beyond sublethal damage, stress response pathways are activated such as the ER-stress pathway with disruption of Ca2+ homeostasis and unfolded protein response. This leads either to apoptosis or autophagic cell death, dependent on the availability of Bax/Bak. Apoptosis triggered directly at the mitochondria or by the ER-stress response is executed via the mitochondrial pathway, whereas in some cases, the receptor-mediated pathway is preferred. If the damage is too severe, the cellular energy level low and /or the cytoplasma membrane leaky, cells will die necrotically. The different modes of cellular responses depend mainly on the PDT-protocol, photosensitizer localisation, cellular damage protection and the available intracellular energy.
University of Salzburg, Department of Molecular Biology, Hellbrunnerstr. 34, 5020 Salzburg, Austria. barbara.krammer@sbg.ac.at
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D000818:Animals; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010569:Perylene / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
D000873:Anthracenes; D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D010569:Perylene; C004965:hypericin