Concomitant treatment with temozolomide enhances apoptotic cell death in glioma cells induced by photodynamic therapy with talaporfin sodium

• NPe6-PDT induced cell death was enhanced by concomitant treatment with temozolomide.
• Adjuvant treatment with temozolomide was not enhanced the NPe6-PDT-induced cell death.
• Intracellular amount of NPe6 was increased by concomitant temozolomide.
• Generation of reactive oxygen species was increased by concomitant temozolomide.

SummaryBackgroundPhotodynamic therapy (PDT) induces selective cell death of neoplastic tissue and connecting vasculature by combining photosensitizers with light. We have previously reported that PDT induces apoptotic cell death in glioma cells when the photosensitizer talaporfin sodium (NPe6) is used. Here, we investigated the combined effect of NPe6-PDT with temozolomide, a DNA-alkylating drug used in glioma therapy.MethodsHuman glioblastoma T98G cells and human glioma U251 cells were used as glioma cells. Cell viability was evaluated by WST-8 assay. Apoptosis was evaluated by measurement of caspase-3 activity and DNA-fragmentation. Intracellular reactive oxygen species were evaluated by dihydrorhodamine assay.ResultsWhile the degree of NPe6-PDT induced cell death unchanged in T98G and U251 cells when temozolomide treatment was adjuvant, it was dose-dependently increased by concomitant treatment with temozolomide. Further, concomitantly administered temozolomide dose-dependently increased caspase-3 activity and DNA-fragmentation, while adjuvant-temozolomide did not. These results are suggesting that concomitantly administered temozolomide potentiates the effect of NPe6-PDT to facilitate apoptotic cell death. Additionally, concomitantly administered temozolomide increased intracellular NPe6-fluorescence and reactive oxygen species, suggesting that the augmentation effect of combined treatment may be due to increased intracellular accumulation of NPe6.ConclusionThese results suggest that concomitant treatment with NPe6-PDT and temozolomide is a potentially useful therapy for glioma.