Role of mitochondria in cell death induced by Photofrin R®—PDT and ursodeoxycholic acid by means of SLIM
Role of mitochondria in cell death induced by Photofrin R®—PDT and ursodeoxycholic acid by means of SLIM
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线粒体在 Photofrin R®—PDT 和熊去氧胆酸 SLIM 诱导细胞死亡中的作用
DOI：
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发表时间：
2007
影响因子：
3.1
通讯作者：
A. Rück
中科院分区：
文献类型：
--
作者：
I. Kinzler;E. Haseroth;C. Hauser;A. Rück
本研究旨在寻找提高光动力疗法（PDT）疗效的新途径。我们研究了光敏剂Photofrin®和熊去氧胆酸（UDCA）的联合作用。UDCA是一种相对无毒的胆汁酸，阿利亚用于治疗胆汁淤积性疾病，据报道可增强其他两种光敏剂的PDT效率。由于除了坏死和自噬过程之外，已经发现细胞凋亡是培养物中许多细胞响应PDT的细胞死亡的主要形式，因此进行了几种适当的测试，例如细胞色素c释放、半胱天冬酶活化和DNA片段化。此外，光谱分辨荧光寿命成像（SLIM）用于分析Photofrin®的细胞组成和呼吸链酶的状态。我们对两种人肝母细胞瘤细胞系的实验显示，Photofrin®与UDCA的组合显著增强了PDT对两种细胞系的功效，尽管Photofrin®作用模式的潜在分子机制似乎在一定程度上不同。在HepG 2细胞中，细胞死亡显然是线粒体紊乱的结果，如细胞色素c释放和DNA片段化所示，而在Huh 7细胞中未观察到这些特征。在这种情况下，其他机制似乎更重要。当UDCA也应用时，PDT效应增强的一个原因可能是UDCA使线粒体膜不稳定。这可以从呼吸链酶的荧光寿命得出结论，在HepG 2细胞中存在UDCA的情况下，呼吸链酶的荧光寿命更长，表明线粒体膜的扰动。因此，PDT损伤线粒体膜的阈值较低，并且与PDT后观察到的增强的细胞色素c释放相关。因此，强化的光损伤导致细胞活力的更高损失。
The present study was undertaken to find new ways to improve efficacy of photodynamic therapy (PDT). We investigated the combinatory effect of the photosensitizer Photofrin® and ursodeoxycholic acid (UDCA). UDCA is a relatively non-toxic bile acid which is used inter alia as a treatment for cholestatic disorders and was reported to enhance PDT efficiency of two other photosensitizers. Since besides necrosis and autophagic processes apoptosis has been found to be a prominent form of cell death in response to PDT for many cells in culture, several appropriate tests, such as cytochrome c release, caspase activation and DNA fragmentation were performed. Furthermore spectral resolved fluorescence lifetime imaging (SLIM) was used to analyse the cellular composition of Photofrin® and the status of the enzymes of the respiratory chain. Our experiments with two human hepatoblastoma cell lines revealed that the combination of Photofrin® with UDCA significantly enhanced efficacy of PDT for both cell lines even though the underlying molecular mechanism for the mode of action of Photofrin® seems to be different to some extent. In HepG2 cells cell death was clearly the consequence of mitochondrial disturbance as shown by cytochrome c release and DNA fragmentation, whereas in Huh7 cells these features were not observed. Other mechanisms seem to be more important in this case. One reason for the enhanced PDT effect when UDCA is also applied could be that UDCA destabilizes the mitochondrial membrane. This could be concluded from the fluorescence lifetime of the respiratory chain enzymes which turned out to be longer in the presence of UDCA in HepG2 cells, suggesting a perturbation of the mitochondrial membrane. The threshold at which PDT damages the mitochondrial membrane was therefore lower and correlated with the enhanced cytochrome c release observed post PDT. Thus enforced photodamage leads to a higher loss of cell viability.
卟啉与外周型苯二氮卓受体相互作用的表征。
影响因子：
3.6
作者：
Verma,A;Snyder,SH
通讯作者：
Snyder,SH
DOI：
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发表时间：
2000
期刊：
Cancer research.
影响因子：
--
作者：
Kessel,D;Caruso,JA;ReinersJr,JJ
通讯作者：
ReinersJr,JJ
影响因子：
11.2
作者：
Gomer,CJ;Rucker,N;Murphree,AL
通讯作者：
Murphree,AL