Yumita Nagahiko, Iwase Yumiko, Watanabe Takahiro, Nishi Koji, Kuwahara Hiroyuki, Shigeyama Masato, Sadamoto Kiyomi, Ikeda Toshihiko, Umemura Shin-Ichiro
Yokohama College of Pharmacy, Yokohama, Kanagawa, Japan
Yokohama College of Pharmacy, Yokohama, Kanagawa, Japan.
Anticancer Res. 2014 Nov;34(11):6481-7.
BACKGROUND/AIM: Sonodynamic cancer therapy is based on the preferential uptake and/or retention of a sonosensitizing drug (sonosensitizer) in tumor tissues and subsequent activation of the drug by ultrasound irradiation. In the present study, we investigated the participation of lipid peroxidation in the mechanism of the sonodynamically-induced antitumor effect with functionalized fullerenes, such as polyhydroxy fullerene (PHF.
Ultrasonically-induced cell damage and lipid peroxidation with PHF were compared in the same in vitro insonation setup. Sarcoma 180 cells suspended in PBS were exposed to 2 MHz ultrasound in the presence and absence of PHF. Cell viability was determined by the Trypan Blue exclusion test. Lipid peroxidation in cell membranes was estimated by measuring the amount of malondialdehyde as the thiobarbituric acid-reactive-substances.
Significant enhancement of the rates of both ultrasonically-induced cell damage and lipid peroxidation was observed in the presence of PHF, both of which were positively correlated with PHF. The enhancement of cell damage and lipid peroxidation with PHF was suppressed by reactive oxygen scavengers such as histidine and tryptophan.
The good correlation observed in the presence of PHF suggests that membrane lipid peroxidation is one of the important intermediary events in sonodynamically-induced cellular damage. The inhibitory effects of histidine and tryptophan also provide evidence that singlet oxygen plays an important role in PHF-mediated sonosensitization of membranes and that this moiety may be an important mediator of cell destruction in sonodynamic therapy associated with PHF and ultrasound.
背景/目的：声动力癌症治疗基于肿瘤组织中声敏化药物（声敏剂）的优先摄取和/或保留，以及随后通过超声照射激活该药物。在本研究中，我们研究了脂质过氧化在功能化富勒烯（如多羟基富勒烯，PHF）介导的声动力抗肿瘤效应机制中的作用。
在相同的体外超声照射装置中，比较了PHF诱导的超声细胞损伤和脂质过氧化。将悬浮于磷酸盐缓冲液（PBS）中的肉瘤180细胞在有或没有PHF的情况下暴露于2MHz超声。通过台盼蓝排斥试验测定细胞活力。通过测量作为硫代巴比妥酸反应性物质的丙二醛量来估计细胞膜中的脂质过氧化。
在存在PHF的情况下，观察到超声诱导的细胞损伤率和脂质过氧化率均显著提高，两者均与PHF呈正相关。PHF引起的细胞损伤和脂质过氧化增强被组氨酸和色氨酸等活性氧清除剂所抑制。
在存在PHF的情况下观察到的良好相关性表明，膜脂质过氧化是声动力诱导细胞损伤的重要中间事件之一。组氨酸和色氨酸的抑制作用也提供了证据表明单线态氧在PHF介导的膜声敏化中起重要作用，并且该部分可能是与PHF和超声相关的声动力治疗中细胞破坏的重要介质。
