Abstract
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.
Keywords: Apoptosis, autophagy, hypericin, molecular, photodynamic therapy, reactive oxygen species, signalling pathway, Hypericin (Hyp), Hypericum species, genotoxicity
Current Medicinal Chemistry
Title: Molecular Response to Hypericin-Induced Photodamage
Volume: 19 Issue: 6
Author(s): B. Krammer and T. Verwanger
Affiliation:
Keywords: Apoptosis, autophagy, hypericin, molecular, photodynamic therapy, reactive oxygen species, signalling pathway, Hypericin (Hyp), Hypericum species, genotoxicity
Abstract: 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.
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Cite this article as:
Krammer B. and Verwanger T., Molecular Response to Hypericin-Induced Photodamage, Current Medicinal Chemistry 2012; 19 (6) . https://dx.doi.org/10.2174/092986712799034842
DOI https://dx.doi.org/10.2174/092986712799034842 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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