Enhancement of Ultrasonically Induced Cell Damage by a Gallium‐Porphyrin Complex, ATX‐70

Abstract

Enhancement of ultrasonically induced cell damage by a gallium‐porphyrin complex [ATX‐70, 2,4‐ bis(l‐decyloxyethyl)‐Ga(III)‐1,3,5,8‐tetramethylporphyrin‐6,7‐dipropionyl diaspartic acid] was investigated. The rate of damage to isolated sarcoma 180 cells in air‐saturated suspension induced by 2 MHz ultrasound irradiation was enhanced more than four times by 80 μM ATX‐70 in contrast to only twice by the same concentration of hematoporphyrin (Hp). The enhancement was almost completely inhibited in the presence of 10 mM histidine in the suspension, but not at all by 100 mM mannitol, which suggests that the enhanced cell damage was mostly mediated by singlet oxygen. Ultrasonically induced active oxygen generation in an air‐saturated aqueous solution of ATX‐70 was studied by detecting the electron spin resonance signals of 2,2,6,6,‐tetramethyl‐4‐piperidone‐N‐oxyl produced by the reaction of 2,2,6,6‐tetramethyl‐4‐piperidone with the generated active oxygen species. The rate of ultrasonically induced nitroxide generation was enhanced five times by 80 μM ATX‐70 in contrast to only twice by Hp. The enhancement was inhibited significantly in the presence of 10 mM histidine in the suspension, but not at all by 100 mM mannitol. The singlet oxygen generation in air‐saturated aqueous solution was further confirmed by the bleaching of N, N‐dimethyl‐4‐nitrosoaniline in the presence of imidazole. The ultrasonically induced bleaching rate was enhanced six times by ATX‐70, in contrast to only twice by Hp.

Sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species

“…Loss of DPBF absorbance at about 410 nm represented the production of singlet oxygen. 18,19 DPBF was dissolved in anhydrous alcohol and attenuated by saline to 0.2 mM. DVDMS 10 µM and hematoporphyrin, protoporphyrin IX, and Photofrin II dissolved in 0.2 mM DPBF were irradiated by laser light (excitation wavelength 635 nm, energy power 5 J), and absorbance of DPBF at 414 nm was monitored using an ultraviolet spectrophotometer.…”

“…Many sonosensitizers are derived from photosensitizers that have been used widely in photodynamic therapy. To date, many conventional photosensitizers, eg, hematoporphyrin, [14][15][16] Photofrin II, 7,17 ATX-70, 18,19 chlorin e6, 20 and ATX-S10, 21 have been confirmed to trigger cell death after activation by ultrasound. Therefore, development of photosensitizers may be an indirect way of identifying sonosensitizers.…”

The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages

“…Fortunately, an alternative therapy exists: low-intensity ultrasound can penetrate deeply into tissues due to its much lower attenuation coefficient in tissues compared with lasers. [7][8][9][10][11] To resolve the problem of penetration depth, we made use of low-intensity ultrasound as a substitute for light in this study.…”

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)

“…Recently, we found that photochemically active porphyrins such as hematoporphyrin, Porfimer Sodium (PF) and a gallium porphyrin complex, 7,12-bis(1-decyloxyethyl)-Ga(III)-3,8,13,17-tetramethylporphyrin 2,18-dipropionyl diaspartic acid (ATX-70) can induce significant cell damage when activated by ultrasound [8,9]. When implanted murine tumors are treated after the administration of such chemicals, tumor growth is significantly inhibited at intensity where ultrasound alone shows only a slight inhibitory effect [10][11][12].…”