| pubmed-article:19421008 | 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. | lld:pubmed |
