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Photodynamic therapy using talaporfin sodium induces concentration-dependent programmed necroptosis in human glioblastoma T98G cells

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Abstract

Photodynamic therapy (PDT) using photosensitizer induces several types of cell death, such as apoptosis, necrosis, and autophagy, depending on the PDT procedure, photosensitizer type, and cell type. We previously demonstrated that PDT using the photosensitizer talaporfin sodium (mono-l-aspartyl chlorine e6, NPe6; NPe6-PDT) induces both mitochondrial apoptotic and necrotic cell death in human glioblastoma T98G cells. However, details regarding the mechanism of necrosis caused by NPe6-PDT are unclear. Here, we investigated whether or not necroptosis, a recently suggested form of programmed necrosis, is involved in the necrotic cell death of NPe6-PDT-treated T98G cells. Leakage of lactate dehydrogenase (LDH) from the cell layer into conditioned medium was significantly increased by NPe6 (25 and 50 μg/ml)-PDT, indicating that NPe6-PDT induces necrosis in these cells. NPe6 (25 μg/ml)-PDT treatment also induced conversion of microtubule-associated protein 1 light-chain 3 (LC3)-I into phosphatidylethanolamine-conjugated LC3-II accompanying autophagosome formation, indicators of autophagy; however, of note, NPe6 (50 μg/ml)-PDT did not induce such autophagic changes. In addition, both necrostatin-1 (a necroptosis inhibitor) and knockdown of necroptotic pathway-related proteins [e.g., receptor interacting serine-threonine kinase (RIP)-1, RIP-3, and mixed lineage kinase domain-like protein (MLKL)] inhibited leakage of LDH caused by NPe6 (25 μg/ml)-PDT. Taken together, the present findings revealed that NPe6-PDT-induced necrotic cell death is mediated in part by the necroptosis pathway in glioblastoma T98G cells.

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Acknowledgments

Talaporfin sodium (NPe6) was provided by Meiji Seika Pharma Co., Ltd. (Tokyo, Japan). The semiconductor laser irradiation device was provided by Panasonic Healthcare Co., Ltd. (Ehime, Japan).

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The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan

    Yuichi Miki, Keiko Moritake, Chihiro Hironaka & Yasuyuki Fujiwara

  2. Department of Neurosurgery, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku, Tokyo, 160-0023, Japan

    Jiro Akimoto

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  1. Yuichi Miki
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  2. Jiro Akimoto
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  3. Keiko Moritake
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  5. Yasuyuki Fujiwara
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Correspondence to Yasuyuki Fujiwara.

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Miki, Y., Akimoto, J., Moritake, K. et al. Photodynamic therapy using talaporfin sodium induces concentration-dependent programmed necroptosis in human glioblastoma T98G cells. Lasers Med Sci 30, 1739–1745 (2015). https://doi.org/10.1007/s10103-015-1783-9

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  • DOI: https://doi.org/10.1007/s10103-015-1783-9

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