Evidence that photoactivated pheophorbide a causes in human cancer cells a photodynamic effect involving lipid peroxidation

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 IC50 values ranging between 70 and 250 nM. The mechanism of phototoxicity has been investigated in HeLa (IC50 = 150 nM) and HepG2 (IC50 = 95 nM) cells. In both cell lines Pba induces lipid peroxidation, as indicated by a marked increase of malonyldialdehyde and oxidized C11 BODIPY581/591. At high doses (>IC50), Pba arrests cell growth completely by activating apoptosis and/or necrosis, while at low doses (