Document Detail


Evidence that photoactivated pheophorbide a causes in human cancer cells a photodynamic effect involving lipid peroxidation.
MedLine Citation:
PMID:  19421008     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Valentina Rapozzi; Mara Miculan; Luigi E Xodo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-06
Journal Detail:
Title:  Cancer biology & therapy     Volume:  8     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-10-13     Completed Date:  2010-02-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1318-27     Citation Subset:  IM    
Affiliation:
Department of Biomedical Science and Technology, School of Medicine, Udine, Italy.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Carcinoma, Hepatocellular / pathology
Cell Line, Tumor / drug effects
Chlorophyll / analogs & derivatives*,  pharmacology,  radiation effects
Drug Screening Assays, Antitumor
Drug Synergism
Glutathione Transferase / antagonists & inhibitors,  genetics,  physiology
Hela Cells / drug effects
Heme Oxygenase-1 / physiology
Humans
Inhibitory Concentration 50
Lipid Peroxidation / drug effects
Liver Neoplasms / pathology
Neoplasm Proteins / antagonists & inhibitors,  genetics,  physiology
Oxidative Stress
Photochemotherapy*
RNA Interference
RNA, Small Interfering / pharmacology
Radiation-Sensitizing Agents / pharmacology*,  radiation effects
Chemical
Reg. No./Substance:
0/Neoplasm Proteins; 0/RNA, Small Interfering; 0/Radiation-Sensitizing Agents; 1406-65-1/Chlorophyll; 15664-29-6/pheophorbide a; EC 1.14.99.3/HMOX1 protein, human; EC 1.14.99.3/Heme Oxygenase-1; EC 2.5.1.18/GSTA1 protein, human; EC 2.5.1.18/Glutathione Transferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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