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Synthetic Smac peptide enhances the effect of etoposide-induced apoptosis in human glioblastoma cell lines

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Summary

Smac/DIABLO is a mitochondrial protein released into cytosol during the progression of apoptosis. Smac/DIABLO promotes apoptosis by neutralizing the inhibitory effect of the inhibitor of apoptosis proteins (IAPs) on the processing and activity of the effecter of caspase. Here, we generated synthetic Smac peptide which possesses an IAP-binding domain and Drosophila antennapaedia penetration sequence, and examined whether it enhances the effect of the chemotherapeutic agent etoposide in the human glioblastoma cell line. Cellular uptake of Smac peptide in several glioma cell lines was most prominent at 6–12 h after addition. Caspase activity assay showed that our peptide successfully increased the activity of caspase-3 and caspase-9 in etoposide-induced apoptosis. In addition, Smac peptide increased the amount of cleaved PARP (poly ADP-ribose polymerase), but control peptides did not. Moreover, the addition of z-VAD-fmk, a caspase inhibitor, counterbalanced the effect of Smac peptide. Finally, we demonstrated that Smac peptide could enhance the growth inhibition effect of etoposide compared with control peptides. These results suggest that synthetic Smac peptide may be a new molecular targeting anti-tumor therapy for human glioblastoma.

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Acknowledgements

This work was supported in part by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (Grant No.15659337).

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Authors and Affiliations

  1. Department of Neurosurgery, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan

    Katsu Mizukawa, Atsufumi Kawamura, Takashi Sasayama, Kazuhiro Tanaka, Masahito Kamei, Masato Sasaki & Eiji Kohmura

  2. Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, 650-0017, Chuo-ku, Kobe, Japan

    Katsu Mizukawa

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  1. Katsu Mizukawa
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Mizukawa, K., Kawamura, A., Sasayama, T. et al. Synthetic Smac peptide enhances the effect of etoposide-induced apoptosis in human glioblastoma cell lines. J Neurooncol 77, 247–255 (2006). https://doi.org/10.1007/s11060-005-9045-5

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