Induction of programmed cell death in human breast cancer cells by an unsymmetrically alkylated polyamine analogue.

Induction of programmed cell death in human breast cancer cells by an unsymmetrically alkylated polyamine analogue.
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DOI:
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发表时间:
1995-08
期刊:
影响因子:
11.2
通讯作者:
Diane E. McCloskey;R. Casero;P. Woster;N. Davidson
Diane E. McCloskey;R. Casero;P. Woster;N. Davidson
中科院分区:
医学1区
文献类型:
--
作者:
Diane E. McCloskey;R. Casero;P. Woster;N. Davidson

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对具有新型作用机制的抗肿瘤化合物的需求是巨大的。其中一种是最近合成的多胺类似物n1 -乙基- n11 -((环丙基)甲基)-4,8-二氮十一烷(CPENSpm)。将激素依赖型和非依赖型人乳腺癌细胞暴露于0.1-10微米的CPENSpm可导致生长抑制和细胞程序性死亡。DNA分裂成高分子量片段和寡核小体大小的片段,两者都是程序性细胞死亡的特征,被确定为时间和浓度依赖。还证明了天然多胺池的耗竭和类似物的积累。这些数据提供了多胺类似物诱导程序性细胞死亡的第一个证据。
The need for antineoplastic compounds with novel mechanisms of action is great. One such agent is the recently synthesized polyamine analogue N1-ethyl-N11-((cyclopropyl)methyl)-4,8-diazaundecane (CPENSpm). Exposure of hormone-dependent and -independent human breast cancer cells to 0.1-10 microM CPENSpm led to both growth inhibition and induction of programmed cell death. Fragmentation of DNA to high molecular weight fragments and oligonucleosomal-sized fragments, both characteristic of programmed cell death, was determined to be time and concentration dependent. Depletion of natural polyamine pools and accumulation of the analogue was also demonstrated. These data provide the first evidence that a polyamine analogue induces programmed cell death.