Photodynamic Therapy in Combination with Talaporfin Sodium Induces Mitochondrial Apoptotic Cell Death Accompanied with Necrosis in Glioma Cells
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概要
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Photodynamic therapy (PDT) induces selective cell death of neoplastic tissue and connecting vasculature by combining photosensitizers with light. Here we clarified the types of cell death induced by PDT in combination with the photosensitizer talaporfin sodium (mono-L-aspartyl chlorine e6, NPe6) in order to evaluate the potential of this therapy as a treatment for glioma. PDT with NPe6 (NPe6-PDT) induces dose-dependent cell death in human glioblastoma T98G cells. Specifically, cell death modalities were observed in NPe6-PDT treated T98G cells, including signs of apoptosis (activation of caspase-3, expression of phosphatidylserine, and DNA fragmentation) and necrosis (stainability of propidium iodide). In addition, high doses of NPe6-PDT decreased the proportion of apoptotic cell death, while increasing necrosis. Closer examination of apoptotic characteristics revealed release of cytochrome-c from mitochondria as well as activation of both caspse-9 and caspase-3 in cells treated with low doses of NPe6-PDT. Z-LEHD-fmk, a caspase-9 specific inhibitor, and Z-DQMD-fmk, a caspase-3 specific inhibitor, showed dose-dependent prevention of cell death in NPe6-PDT treated cells, indicating that mitochondrial apoptotic pathway was a factor in the observed cell death. Further, the cell morphology was observed after PDT. Time- and NPe6-dose dependent necrotic features were increased in NPe6-PDT treated cells. These results suggest that NPe6-PDT could be an effective treatment for glioma if used in mild doses to avoid the increased necrosis that may induce undesirable obstacles.
著者
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Hirano Kazuya
School Of Pharmacy Tokyo University Of Pharmacy And Life Sciences
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Beppu Masatoshi
School Of Pharmacy Tokyo Univ. Of Pharmacy And Life Sciences
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Haraoka Jo
Department Of Neurosurgery Tokyo Medical College Tokyo
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Akimoto Jiro
Department Of Neurosurgery Tokyo Medical University
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Miki Yuichi
School Of Pharmacy Tokyo University Of Pharmacy And Life Sciences
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Tsutsumi Masateru
Department Of Neurosurgery Tokyo Medical University
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Hirano Kazuya
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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Beppu Masatoshi
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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Yokoyama Sakino
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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Homma Tomomi
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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