Open AccessSonodynamically‐induced apoptosis, necrosis, and active oxygen generation by mono‐l‐aspartyl chlorin e6
Author(s) -
Yumita Nagahiko,
Han QingSong,
Kitazumi Ikuko,
Umemura Shinichiro
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00653.x
Subject(s) - apoptosis , necrosis , dna fragmentation , chemistry , ultrasound , chlorin , caspase 3 , microbiology and biotechnology , fragmentation (computing) , programmed cell death , cancer research , photodynamic therapy , biochemistry , pathology , biology , medicine , ecology , radiology , organic chemistry
In this study, we investigated the induction of apoptosis by ultrasound in the presence of a photochemically active chlorine, mono‐l‐aspartyl chlorin e6 (NPe6). HL‐60 cells were exposed to ultrasound for up to 3 min in the presence and absence of NPe6, and the induction of apoptosis was examined by analyzing cell morphology, DNA fragmentation, and caspase‐3 activity. Cells treated with 80 µM NPe6 and ultrasound clearly showed membrane blebbing and cell shrinkage, whereas significant morphologic changes were not observed in cells exposed to either ultrasound alone, at the same intensity, or NPe6 alone. Also, DNA ladder formation and caspase‐3 activation were observed in cells treated with both ultrasound and NPe6 but not in cells treated with ultrasound or NPe6 alone. In addition, NPe6 substantially enhanced nitroxide generation by ultrasound in the same acoustical arrangement. Sonodynamically‐induced apoptosis, caspase‐3 activation, and nitroxide generation were significantly suppressed by histidine. These results suggest that the combination of ultrasound and NPe6 sonochemically induces apoptosis as well as necrosis in HL‐60 cells. They further suggest that some ultrasonically‐generated active species, deactivatable by histidine, are the major mediators to induce the observed apoptosis. ( Cancer Sci 2008; 99: 166–172)