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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2009-10-13
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1555-8576
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1318-27
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
pubmed:year
2009
pubmed:articleTitle
Evidence that photoactivated pheophorbide a causes in human cancer cells a photodynamic effect involving lipid peroxidation.
pubmed:affiliation
Department of Biomedical Science and Technology, School of Medicine, Udine, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't