Source:http://linkedlifedata.com/resource/pubmed/id/19421008
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
14
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pubmed:dateCreated |
2009-10-13
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pubmed:abstractText |
Photodynamic therapy (PDT) is a treatment modality that uses a combination of a photosensitizer and light to induce a photokilling process in the tumor tissue. Recently we re-considered pheophorbide a (Pba), a second-generation photosensitizer that has not yet been thoroughly investigated. Here, we report that Pba irradiated at 14 J/cm(2) induces a strong photodynamic effect in four tumor cell lines, with IC(50) values ranging between 70 and 250 nM. The mechanism of phototoxicity has been investigated in HeLa (IC(50) = 150 nM) and HepG2 (IC(50) = 95 nM) cells. In both cell lines Pba induces lipid peroxidation, as indicated by a marked increase of malonyldialdehyde and oxidized C11 BODIPY(581/591). At high doses (>IC(50)), Pba arrests cell growth completely by activating apoptosis and/or necrosis, while at low doses (<IC(50)), the photosensitizer causes a temporary growth arrest. In the presence of Pba photodamage, the cells activate a protective mechanism against oxidative stress mediated by a strong increase of heme oxygenase-1 expression (up to 12-fold in HepG2 and 25-fold in HeLa). Moreover, considering that GSTA1-1 is a response gene to lipid peroxidation, we treated with Pba a genetically modified HepG2 clone, in which GSTA1-1 was constitutively silenced by siRNA, observing a 25% increase of lipid peroxidation as compared to HepG2 clone expressing GSTA1-1. These data suggest that combine treatments in which Pba is used with gene-silencing molecules against HO-1 and GSTA1-1 should potentiate PDT.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chlorophyll,
http://linkedlifedata.com/resource/pubmed/chemical/GSTA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/HMOX1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase-1,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Radiation-Sensitizing Agents,
http://linkedlifedata.com/resource/pubmed/chemical/pheophorbide a
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1555-8576
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1318-27
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pubmed:meshHeading |
pubmed-meshheading:19421008-Apoptosis,
pubmed-meshheading:19421008-Carcinoma, Hepatocellular,
pubmed-meshheading:19421008-Cell Line, Tumor,
pubmed-meshheading:19421008-Chlorophyll,
pubmed-meshheading:19421008-Drug Screening Assays, Antitumor,
pubmed-meshheading:19421008-Drug Synergism,
pubmed-meshheading:19421008-Glutathione Transferase,
pubmed-meshheading:19421008-HeLa Cells,
pubmed-meshheading:19421008-Heme Oxygenase-1,
pubmed-meshheading:19421008-Humans,
pubmed-meshheading:19421008-Inhibitory Concentration 50,
pubmed-meshheading:19421008-Lipid Peroxidation,
pubmed-meshheading:19421008-Liver Neoplasms,
pubmed-meshheading:19421008-Neoplasm Proteins,
pubmed-meshheading:19421008-Oxidative Stress,
pubmed-meshheading:19421008-Photochemotherapy,
pubmed-meshheading:19421008-RNA, Small Interfering,
pubmed-meshheading:19421008-RNA Interference,
pubmed-meshheading:19421008-Radiation-Sensitizing Agents
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pubmed:year |
2009
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pubmed:articleTitle |
Evidence that photoactivated pheophorbide a causes in human cancer cells a photodynamic effect involving lipid peroxidation.
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pubmed:affiliation |
Department of Biomedical Science and Technology, School of Medicine, Udine, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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