Ultrasound-induced apoptosis in the presence of Sonazoid and associated alterations in gene expression levels: a possible therapeutic application.
Ultrasound (US) has been shown to induce apoptosis and cell lysis in cancer cells. In this study, we report on the potential of using Sonazoid, a new echo-contrast agent, that is chemically more stable and US-resistant in combination with US in cancer therapy. The biological effects and their mechanisms in the presence or absence of ultrasonic exposure in vitro were investigated. In addition, the impact of the agent on the expression levels of genes responsive to US was studied using global-scale microarrays and computational gene expression analysis tools. Our results show that the combination led to enhanced cell killing in the presence of 1 MHz acoustic field. The apoptosis induction was shown to be mediated by the mitochondrial pathway. The occurrence of US-induced DNA damage was also observed. Despite these findings, the agent at concentrations similar to those clinically used can be considered as well tolerated. Furthermore, Sonazoid enhanced expression of genes that related to apoptosis and are responsive to US, although it alone had almost no effect. These results indicate the potential of Sonazoid for US contrast enhancement as well as the possibility of its use in US-aided therapies.
Furusawa
Yukihiro
Y
Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
Zhao
Qing-Li
QL
Hassan
Mariame Ali
MA
Tabuchi
Yoshiaki
Y
Takasaki
Ichiro
I
Wada
Shigehito
S
Kondo
Takashi
T
D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019295:Computational Biology; D003287:Contrast Media / Q000494:pharmacology*; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000494:pharmacology*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D053263:Gene Regulatory Networks; D006657:Histones / Q000378:metabolism; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D007501:Iron / Q000494:pharmacology*; D008223:Lymphoma / Q000235:genetics / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010087:Oxides / Q000494:pharmacology*; D010766:Phosphorylation; D013010:Sonication; D020298:U937 Cells; D014464:Ultrasonic Therapy
D003287:Contrast Media; D005290:Ferric Compounds; C468783:H2AX protein, human; D006657:Histones; D010087:Oxides; C069727:Sonazoid; D017665:Hydroxyl Radical; D007501:Iron