Differential cytotoxicity and sonosensitization by sanazole: effect of cell type and acoustic parameters.
OBJECTIVE
Although sanazole has been used as a hypoxic radiosensitizer, we recently reported on its ability to sensitize U937 cells to hyperthermia and X-irradiation under aerobic conditions, enhancing apoptotic cell death following the combined treatment. The current study was undertaken to evaluate the effect of sanazole as a sonosensitizer under previously studied acoustic conditions of different pulse repetition frequencies, using two cell lines representative of solid tumours and haematopoietic cancers.


METHODS
Cells were treated with different doses of sanazole. Flow-cytometric analysis and DNA fragmentation assay were carried out at different times, and morphological features were also inspected. For ultrasound treatment, cells were pre-incubated with a non-cytotoxic dose of sanazole for 30 min before exposure. Evaluation of cell killing and a parallel examination of intracellular oxidative stress levels in both cell lines were performed using flow cytometry.


RESULTS
Sanazole alone displayed selective cytotoxic effects towards solid tumour-derived cancer cells, resulting in complete cell death after 24 h of treatment, and enhanced the ultrasound-induced cell killing 6 h post-treatment. The enhancement seemed to be mediated by an additive increase in intracellular oxidative stress levels.


CONCLUSIONS
Sanazole seems to be an efficient cytotoxic agent for the treatment of solid tumours and a promising sonosensitizer under aerobic conditions.
Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan.|Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr Al-Aini str., 11562, Cairo, Egypt.
Mariame A
MA
Hassan
Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan.
Yukihiro
Y
Furusawa
Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan.
Qing-Li
QL
Zhao
Division of Molecular Genetic Research, Life Science Research Center, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan.
Ichiro
I
Takasaki
Department of Anatomy, School of Medicine, Fukuoka University, Nanakuma, Fukuoka, 814-0180, Japan.
Loreto B
LB
Feril
Department of Anatomy, School of Medicine, Fukuoka University, Nanakuma, Fukuoka, 814-0180, Japan.
Katsuro
K
Tachibana
Laboratory of Biomedical Instrumentation and Measurement, Graduate School of Information Science and Technology, Hokkaido University, Sapporo, 060-0814, Japan.
Nobuki
N
Kudo
Department of Gastroenterology and Hematology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan.
Masami
M
Minemura
Department of Gastroenterology and Hematology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan.
Toshiro
T
Sugiyama
Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan. kondot@med.u-toyama.ac.jp.
Takashi
T
Kondo
Apoptosis; Pulse repetition frequency; Sanazole; Sonosensitizer; Ultrasound