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.

2007-09-10·Cancer Chemotherapy and Pharmacology4区 · 医学

Sonodynamic therapy on chemically induced mammary tumor: pharmacokinetics, tissue distribution and sonodynamically induced antitumor effect of gallium–porphyrin complex ATX-70

4区 · 医学

Article

作者: Nobuo Okuyama ; Kazuaki Sasaki ; Nagahiko Yumita ; Shin-ichiro Umemura

Sonodynamically induced antitumor effect of a gallium porphyrin complex, ATX-70 was evaluated on a chemically induced mammary tumor in Sprague-Dawley rats. The timing of 24 h after the administration of ATX-70 was chosen for ultrasonic exposure, based on pharmacokinetic analysis of ATX-70 concentrations in the tumor, plasma, skin, and muscle. At an ATX-70 dose not less than 2.5 mg/kg and at a free-field ultrasonic intensity not less than 3 W/cm(2), the synergistic effect between ATX-70 administration and ultrasonic exposure on the tumor growth inhibition was significant. These results suggest that ATX-70 is a potential sonosensitizer for sonodynamic treatment of spontaneous mammary tumors.

2004-09-01·Ultrasound in Medicine & Biology3区 · 医学

Sonodynamic treatment of murine tumor through second-harmonic superimposition

3区 · 医学

Article

作者: Kazuaki Sasaki ; Shin Ichiro Umemura ; Ken Ichi Kawabata ; Nagahiko Yumita

Acoustic cavitation is the primary mechanism of sonochemical reaction and has potential use for tumor treatment in combination with a certain sonodynamically active agent. It has been known that inducing cavitation with progressive waves is more difficult than with standing waves. This may have been limiting the sonodynamic treatment of tumors. We found that ultrasonically induced chemical reactions are greatly accelerated when the second harmonic is superimposed onto the fundamental. Experimental murine tumors were treated with progressive waves in combination with administration of a gallium-porphyrin complex (ATX-70). The tumors treated with second-harmonic superimposition stopped growing for about 2 days and then gradually started growing again. When only 0.5 MHz was used, tumor growth was not significantly different from that in untreated tumors. It was significantly slower than the untreated when only 1.0 MHz was used, but it was significantly further slowed when second-harmonic superimposition was used. The tumor-bearing mice treated with second-harmonic superimposition after ATX-70 administration survived 5 days longer on average than those untreated.

100 项与 ATX-70 相关的药物交易

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