RRC ID 44183
著者 Miki Y, Akimoto J, Yokoyama S, Homma T, Tsutsumi M, Haraoka J, Hirano K, Beppu M.
タイトル Photodynamic therapy in combination with talaporfin sodium induces mitochondrial apoptotic cell death accompanied with necrosis in glioma cells.
ジャーナル Biol Pharm Bull
Abstract 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. Benziloxycarbonyl-Leu-Gln(OMe)-His-Asp(OMe)-fluoromethyl-ketone (Z-LEHD-fmk), a caspase-9 specific inhibitor, and benziloxycarbonyl-Asp(OMe)-Gln-Met-Asp(OMe)-fluoromethyl-ketone (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.
巻・号 36(2)
ページ 215-21
公開日 2013-1-1
DOI 10.1248/bpb.b12-00567
PII DN/JST.JSTAGE/bpb/b12-00567
PMID 23196427
MeSH Antineoplastic Agents / administration & dosage* Brain Neoplasms / drug therapy* Brain Neoplasms / metabolism Brain Neoplasms / pathology Caspase 3 / metabolism Cell Death / drug effects Cell Line, Tumor Cytochromes c / metabolism DNA Fragmentation Glioma / drug therapy* Glioma / metabolism Glioma / pathology Humans Mitochondria / drug effects Mitochondria / metabolism Necrosis / chemically induced Necrosis / metabolism Necrosis / pathology Photochemotherapy* Photosensitizing Agents / administration & dosage* Porphyrins / administration & dosage*
IF 1.863
引用数 19
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 T98G(RCB1954)