Antioxidant inhibitors potentiate the cytotoxicity of photodynamic therapy

Photodynamic therapy (PDT) is an increasingly popular anticancer treatment that uses photosensitizer, light, and tissue oxygen to generate cytotoxic reactive oxygen species (ROS) within illuminated cells. Acting to counteract ROS-mediated damage are various cellular antioxidant pathways. In this study, we combined PDT with specific antioxidant inhibitors to potentiate PDT cytotoxicity in MCF-7 cancer cells. We used disulphonated aluminium phthalocyanine photosensitizer plus various combinations of the antioxidant inhibitors: diethyl-dithiocarbamate (DDC, a Cu/Zn-SOD inhibitor), 2-Methoxyestradiol (2-ME, a Mn-SOD inhibitor), L-buthionine sulfoximine (BSO, a glutathione synthesis inhibitor) and 3-amino-1,2,4-Triazole (3-AT, a catalase inhibitor). BSO, singly or in combination with other antioxidant inhibitors, significantly potentiated PDT cytotoxicity, corresponding with increased ROS levels and apoptosis. The greatest potentiation of cell death over PDT alone was seen when cells were pre-incubated for 24 hours with 300 ?M BSO plus 10 mM 3-AT (1.62-fold potentiation) or 300 ?M BSO plus 1 ?M 2-ME (1.52-fold), or with a combination of all four inhibitors (300 ?M BSO, 10 mM 3-AT, 1 ?M 2-ME, 10 ?M DDC: 1.4-fold). Because many of these inhibitors have already been clinically tested, this work facilitates future in vivo studies.