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

Nagahiko Yumita, Kazuho Okudaira, Yasunori Momose, Shinichiro Umemura

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1071-1078
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume66
Issue number6
DOIs
Publication statusPublished - 2010 Nov 1

Keywords

  • ATX-70
  • Apoptosis
  • HL-60 cells
  • Sonodynamic therapy
  • Ultrasound

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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