Key Laboratory of Foresty Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, People's Republic of China.
Planta Med. 2011 Jul;77(10):1005-12. doi: 10.1055/s-0030-1270732. Epub 2011 Feb 3.
7-Xylosyl-10-deacetylpaclitaxel is a natural hydrophilic paclitaxel derivative. It has long been used in Chinese clinics to treat cancer. In order to further explore the underlying intracellular target of 7-xylosyl-10-deacetylpaclitaxel towards the PC-3 cell line, the ultra-structural morphology of mitochondria, the intracellular Ca (2+), the intracellular ATP, the intracellular hydrogen peroxide and pro-apoptotic Bax and Bcl-2 protein expression were measured. Additionally, the changes of mitochondrial morphology and membrane potential ( ΔΨm) were analyzed by atomic force microscopy (AFM) and flow cytometry, respectively. Our results suggest that the intracellular target of 7-xylosyl-10-deacetylpaclitaxel may be the mitochondrial permeability transition pore (mPTP). To further evaluate this hypothesis, we assessed the effect of a specific mPTP inhibitor (cyclosporine A) on the toxic action of 7-xylosyl-10-deacetylpaclitaxel. The 7-xylosyl-10-deacetylpaclitaxel-induced decrease in mitochondrial inner transmembrane potential (ΔΨm) was abolished by the addition of cyclosporine A (CsA) in PC-3 cells, indicating that 7-xylosyl-10-deacetylpaclitaxel may target mPTP. Furthermore, treatment with 7-xylosyl-10-deacetylpaclitaxel increased ROS levels in PC-3 cells. This effect was counteracted by 10 µM cyclosporine A. These data indicate that oxidative damage is involved in mPTP.
7-木糖基-10-去乙酰紫杉醇是一种天然亲水性紫杉醇衍生物。它在中国临床中已长期用于治疗癌症。为了进一步探讨 7-木糖基-10-去乙酰紫杉醇对 PC-3 细胞系的潜在细胞内靶点，我们测量了线粒体的超微形态结构、细胞内 Ca(2+)、细胞内 ATP、细胞内过氧化氢以及促凋亡 Bax 和 Bcl-2 蛋白的表达。此外，我们还通过原子力显微镜（AFM）和流式细胞术分别分析了线粒体形态和膜电位（ΔΨm）的变化。结果表明，7-木糖基-10-去乙酰紫杉醇的细胞内靶点可能是线粒体通透性转换孔（mPTP）。为了进一步验证这一假说，我们评估了特定 mPTP 抑制剂（环孢菌素 A）对 7-木糖基-10-去乙酰紫杉醇毒性作用的影响。在 PC-3 细胞中，7-木糖基-10-去乙酰紫杉醇诱导的线粒体内膜电位（ΔΨm）下降被环孢菌素 A（CsA）的加入所消除，这表明 7-木糖基-10-去乙酰紫杉醇可能靶向 mPTP。此外，用 7-木糖基-10-去乙酰紫杉醇处理可增加 PC-3 细胞中的 ROS 水平。这一作用可被 10µM 环孢菌素 A 拮抗。这些数据表明氧化损伤参与 mPTP。
