title: Sonodynamically induced apoptosis and active oxygen generation by gallium-porphyrin complex, ATX-70.
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.
authors.affiliation: Yokohama College of Pharmacy, 601, Matano-cho, Totsuka-ku, Yokohama, Kanagawa 245-0066, Japan. n.yumita@hamayaku.ac.jp
authors.forename: Nagahiko
authors.initials: N
authors.lastname: Yumita
authors.forename: Kazuho
authors.initials: K
authors.lastname: Okudaira
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Momose
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Umemura
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation; D004338:Drug Combinations; D004578:Electron Spin Resonance Spectroscopy; D004586:Electrophoresis; D004789:Enzyme Activation / Q000187:drug effects; D005708:Gallium / Q000494:pharmacology; D018922:HL-60 Cells / Q000000981:diagnostic imaging* / Q000187:drug effects*; D006639:Histidine / Q000378:metabolism; D006801:Humans; D009589:Nitrogen Oxides / Q000378:metabolism; D011166:Porphyrins / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014464:Ultrasonic Therapy / Q000379:methods; D014463:Ultrasonography
chemical_list: D004338:Drug Combinations; D009589:Nitrogen Oxides; D011166:Porphyrins; D017382:Reactive Oxygen Species; C081908:ATX 70; D006639:Histidine; D005708:Gallium; D053148:Caspase 3; C039900:nitroxyl