Abstract
Photodynamic therapy (PDT) is a novel and promising cancer treatment which employs a combination of a photosensitizing chemical and visible light to induce apoptosis in cancer cells. Singlet oxygen has been recognized as the main origin of oxidative stress in PDT. However, the precise mechanism of PDT-induced apoptosis is not well characterized, especially the dualistic role of nitric oxide (NO). To dissect the apoptosis pathways triggered by PDT, the intracellular free radicals in MCF-7 cells were investigated by examining a novel photosensitizer 2-butylamino-2-demethoxyhypocrellin B (2-BA-2-DMHB)-mediated PDT. It was found that exposure of the cells to 2-BA-2-DMHB and irradiation resulted in a significant increase of intracellular ROS in minutes, and then followed by cytoplasmic free calcium enhancement, mitochondrial nitric oxide synthase (mtNOS) activation, cytochrome c release, and apoptotic death. Scavengers of singlet oxygen or NO could attenuate PDT-induced cell viability loss, nucleus morphology changes, cytochrome c release, mitochondria swelling, and apo-apoptosis gene p53 and p21 mRNA levels. The results suggested that both ROS and NO played important roles in the apoptosis-induced by PDT.
Copyright 2006 Elsevier Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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Breast Neoplasms / chemistry
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / ultrastructure
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Calcium / analysis
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Calcium / metabolism
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Cell Line, Tumor
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Cell Nucleus / drug effects
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Cell Nucleus / ultrastructure
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Cyclic N-Oxides / pharmacology
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism
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Cytochromes c / antagonists & inhibitors
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Female
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Humans
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Imidazoles / pharmacology
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Mitochondria / chemistry
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Mitochondria / drug effects
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Mitochondria / metabolism
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Mitochondrial Swelling / drug effects
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Nitric Oxide / analysis
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Nitric Oxide / metabolism*
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Perylene / analogs & derivatives*
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Perylene / antagonists & inhibitors
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Perylene / pharmacology
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Perylene / therapeutic use
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Photochemotherapy*
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Photosensitizing Agents / therapeutic use*
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Quinones / antagonists & inhibitors
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Quinones / pharmacology
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Quinones / therapeutic use*
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Reactive Oxygen Species / analysis
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Reactive Oxygen Species / metabolism*
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Sodium Azide / pharmacology
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
Substances
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2-butylamino-2-demethoxy-hypocrellin B
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Cyclic N-Oxides
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Cyclin-Dependent Kinase Inhibitor p21
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Imidazoles
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Photosensitizing Agents
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Quinones
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Reactive Oxygen Species
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Tumor Suppressor Protein p53
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2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide
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Nitric Oxide
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Perylene
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Cytochromes c
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Sodium Azide
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Calcium