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Sonodynamically induced apoptosis and active oxygen generation by gallium–porphyrin complex, ATX-70

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Abstract

In this study, we investigated the induction of apoptosis by ultrasound in the presence of the photochemically active gallium–porphyrin complex, 7,12-bis(1-decyloxyethyl)-Ga(III)-3,8,13,17-tetramethyl-porphyrin 2,18-dipropionyl diaspartic acid (ATX-70). HL-60 cells were exposed to ultrasound for up to 3 min in the presence and absence of ATX-70, and the induction of apoptosis was examined by analyzing cell morphology, DNA fragmentation, and caspase-3 activity. Cells treated with 80 μM ATX-70 and ultrasound clearly showed membrane blebbing and cell shrinkage, whereas significant morphologic changes were not observed in cells exposed to either ultrasound or ATX-70 alone. Also, DNA ladder formation and caspase-3 activation were observed in cells treated with both ultrasound and ATX-70 but not in cells treated with ultrasound or ATX-70 alone. In addition, the combination of ATX-70 and the same acoustical arrangement of ultrasound substantially enhanced nitroxide generation by the cells. Sonodynamically induced apoptosis, caspase-3 activation, and nitroxide generation were significantly suppressed by histidine. These results indicate that the combination of ultrasound and ATX-70 induces apoptosis in HL-60 cells. The significant reduction in sonodynamically induced apoptosis, nitroxide generation, and caspase-3 activation by histidine suggests that active species such as singlet oxygen are important in the sonodynamic induction of apoptosis.

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Authors and Affiliations

  1. Yokohama College of Pharmacy, 601, Matano-cho, Totsuka-ku, Yokohama, Kanagawa, 245-0066, Japan

    Nagahiko Yumita

  2. School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba, 274-8510, Japan

    Kazuho Okudaira & Yasunori Momose

  3. Department of Electrical and Communication Engineering, Tohoku University, Aoba 6-6-05, Aramaki, Aoba-ku, Sendai, 980-8579, Japan

    Shin-ichiro Umemura

Authors
  1. Nagahiko Yumita
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  2. Kazuho Okudaira
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  3. Yasunori Momose
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  4. Shin-ichiro Umemura
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Correspondence to Nagahiko Yumita.

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Yumita, N., Okudaira, K., Momose, Y. et al. Sonodynamically induced apoptosis and active oxygen generation by gallium–porphyrin complex, ATX-70. Cancer Chemother Pharmacol 66, 1071–1078 (2010). https://doi.org/10.1007/s00280-010-1264-6

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  • DOI: https://doi.org/10.1007/s00280-010-1264-6

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