Apoptosis of HL-60 cells induced by sonodynamic therapy with zinc phthalocyanine tetrasulfonate

Nagahiko Yumita, Yumiko Iwase, Koji Nishi, Kenji Onodera, Toshio Fukail, Toshihiko Ikeda, Shin Ichiro Umemura, Yasunori Momose

Research output: Contribution to journalArticlepeer-review


In this study, we investigated the induction of apoptosis by ultrasound in the presence of Zinc Phthalocyanine Tetrasulfonate (ZnPcTS). HL-60 cells were exposed to ultrasound for up to 3 min in the presence and absence of ZnPcTS, and the induction of apoptosis was examined by analyzing cell morphology, DNA fragmentation, and caspase-3 activity. Reactive oxygen species were measured by means of ESR and spin trapping technique. Cells treated with 80 μM ZnPcTS and ultrasound clearly showed membrane blebbing and cell shrinkage, whereas significant morphologic changes were not observed in cells exposed to either ultrasound or ZnPcTS alone. Also, DNA ladder formation and caspase-3 activation were observed in cells treated with both ultrasound and ZnPcTS but not in cells treated with ultrasound or ZnPcTS alone. In addition, the combination of ZnPcTS and the same acoustical arrangement of ultrasound substantially enhanced nitroxide generation. Sonodynamically induced apoptosis, caspase-3 activation, and nitroxide generation were significantly suppressed by histidine. These results indicate that the combination of ultrasound and ZnPcTS induced apoptosis in HL-60 cells. The significant reduction in sonodynamically induced apoptosis, nitroxide generation, and caspase-3 activation by histidine suggests active species such as singlet oxygen are important in the sonodynamic induction of apoptosis. These experimental results support the possibility of sonodynamictreatment for cancer using the induction of apoptosis.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
Issue number5-6
Publication statusPublished - 2012 Jul


  • Apoptosis
  • HL-60
  • Sonodynamic therapy
  • Ultrasound
  • Zinc phthalocyanine tetrasulfonate

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)


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