生化学と分析生化学

概要

Involvement of Reactive Oxygen Species in Sonodynamically Induced Apoptosis by 4-Formyloximeetylidene-3-Hydroxyl-2-Vinyl-euterio-Porphynyl (IX)-6-7-Diaspartic Acid (ATX-S10)

Nagahiko Yumita, Yumiko Iwase, Koji Nishi, Toshihiko Ikeda, Toshio Fukai, Kazuyoshi Takeda, Kenji Onodera, Shin-ichiro Umemura, Kazuho Okudaira and Yasunori Momose

Background: In this study, we investigated the induction of apoptosis by ultrasound in the presence of the
photochemically active chlorine, 4-formyloximeetylidene-3-hydroxyl-2-vinyl-deuterio-porphynyl (IX)-6-7-diaspartic acid (ATX-S10).
Methods: HL-60 cells were exposed to ultrasound for up to 3 min in the presence and absence of ATX-S10, and the induction of apoptosis was examined by analyzing cell morphology, DNA fragmentation, and caspase-3 activity.
Results: Cells treated with 80μM ATX-S10 and ultrasound clearly showed membrane blebbing and cell shrinkage, whereas significant morphologic changes were not observed in cells exposed to either ultrasound or ATX-S10 alone. Also, DNA ladder formation and caspase-3 activation were observed in cells treated with both ultrasound and ATX-S10 but not in cells treated with ultrasound or ATX-S10 alone. In addition, the combination of ATX-S10 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.
Conclusions: These results indicate that the combination of ultrasound and ATX-S10 induces 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.
General significance: The results reported in this paper are experimental, but they significantly support the possibility of sonodynamic treatment for cancer using the induction of apoptosis.