Sequential events of apoptosis involving docetaxel, a microtubule-interfering agent: a cytometric study.
Sequential events of apoptosis involving docetaxel, a microtubule-interfering agent: a cytometric study.
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涉及多西他赛的细胞凋亡的顺序事件，一种微管裂化剂：一项细胞仪研究。
DOI：
10.1186/1471-2121-7-6
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发表时间：
2006-01-26
期刊：
影响因子：
--
通讯作者：
Marini, M
中科院分区：
文献类型：
--
作者：
Fabbri, F;Carloni, S;Brigliadori, G;Zoli, W;Lapalombella, R;Marini, M
尽管对程序性细胞死亡的理解有了很大的进展，但很少有人注意到程序性细胞死亡的发生顺序，特别是对微管干扰剂如紫杉烷类诱导的凋亡过程了解甚少。为了增加这样的知识，我们研究了一些独立的生物化学和细胞学的修改，使用细胞计数的方法在膀胱癌细胞系与第二代紫杉烷，多西他赛治疗。在几个小时内，药物处理诱导线粒体膜转换，细胞收缩和粒度减少。24 h内细胞周期几乎完全阻滞于G2/M期。亚二倍体峰在处理后48小时开始变得突出。同时，DNA梯状条带的出现证明了半胱天冬酶依赖的染色质断裂。同时，发生了特定的细胞表面修饰，首先涉及糖蛋白糖基化和后来的磷脂不对称性。随后通过TUNEL法检测DNA片段化。随着时间的推移，细胞膜变得可渗透碘化丙啶。一个非常相似的时间进程的凋亡事件后，发现用相同的药物治疗的骨髓单核细胞系。在讨论了所用方法的一些特点及其局限性后，提出了一系列凋亡事件，其中线粒体跨膜电位（Δ μ m）的崩溃是凋亡的最早迹象。
Despite the great advances in the understanding of programmed cell death, little attention has been paid to the sequence of the events that characterise it. In particular, the course of apoptotic events induced by microtubule-interfering agents such as taxanes is poorly understood. In order to increase such knowledge, we studied a number of independent biochemical and cytological modifications using cytometric methods in a bladder cancer cell line treated with the second generation taxane, docetaxel. Within a few hours, drug treatment had induced mitochondrial membrane transition, cell shrinkage and a decrease in granularity. Cell cycle was almost completely blocked in G2/M phase within 24 hours. The hypodiploid peak started to become prominent 48 hours after the treatment. At the same time, the appearance of a DNA ladder demonstrated caspase-dependent chromatin fragmentation. Concurrently, specific cell surface modifications took place, involving at first glycoprotein syalilation and later phospholipid asymmetry. DNA fragmentation was subsequently detected by TUNEL assay. Over time, cell membranes became permeable to propidium iodide. A very similar time-course of apoptotic events was found after treatment of a myelomonocytic cell line with the same drug. After discussing some characteristics of the methods employed and their limitations, a succession of apoptotic events over time is suggested, in which the collapse of mitochondrial transmembrane potential (Δψm) is the earliest sign of apoptosis.
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DOI：
10.1093/jnci/83.11.757
发表时间：
1991-06-05
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
MONKS, A;SCUDIERO, D;BOYD, M
通讯作者：
BOYD, M
影响因子：
2.2
作者：
Chiu, L;Cherwinski, H;Dunne, JF
通讯作者：
Dunne, JF
影响因子：
7.7
作者：
Detaille, D;Guigas, B;Leverve, X
通讯作者：
Leverve, X
影响因子：
3.7
作者：
Marini, M;Frabetti, F;Poirier, GG
通讯作者：
Poirier, GG
影响因子：
64.8
作者：
Enari, M;Sakahira, H;Nagata, S
通讯作者：
Nagata, S