P21WAF1/CIP1 is dispensable for G1 arrest, but indispensable for apoptosis induced by sodium butyrate in MCF-7 breast cancer cells
P21WAF1/CIP1 is dispensable for G1 arrest, but indispensable for apoptosis induced by sodium butyrate in MCF-7 breast cancer cells
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DOI：
10.1038/sj.onc.1207020
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发表时间：
2004-01-08
期刊：
影响因子：
8
通讯作者：
Le Bourhis, X
中科院分区：
文献类型：
--
作者：
Chopin, V;Toillon, RA;Le Bourhis, X
丁酸钠（NaB）已被提议作为一种潜在的抗癌剂。然而，其作用机制尚未完全阐明。在这里，我们发现NaB诱导的细胞周期阻滞和凋亡与MCF-7乳腺癌细胞中P21（waf 1/cip 1）的增加有关。免疫荧光分析显示，这种增加在细胞核中更为重要。瞬时转染MCF-7细胞与p21缺陷的相互作用与CDK，但不与p21缺陷的相互作用与PCNA（p21 PCNA-），废除NaB诱导的细胞周期停滞。这表明细胞周期阻滞涉及P21（waf 1/cip 1）与CDK的相互作用。然而，P21（waf 1/cip 1）是无效的，因为p21反义并不改变细胞周期阻滞。而p21反义核酸或p21 PCNA-抑制剂均能阻断NaB诱导的细胞凋亡。此外，NaB降低PCNA水平，但增加PCNA与P21（waf 1/cip 1）的关联。提示NaB诱导的细胞凋亡需要P21（waf 1/cip 1）及其与PCNA的相互作用。
Sodium butyrate (NaB) has been proposed as a potential anticancer agent. However, its mechanism of action is not totally elucidated. Here, we showed that NaB-induced cell cycle arrest and apoptosis were associated with an increase of P21(waf1/cip1) in MCF-7 breast cancer cells. This increase was more important in the nuclei, as revealed by immunofluorescence analysis. Transient transfections of MCF-7 cells with p21 deficient for interaction with CDK, but not with p21 deficient for interaction with PCNA (p21PCNA-), abrogated NaB-induced cell cycle arrest. This indicated that cell cycle blockage involved the interaction of P21(waf1/cip1) with CDK. However, P21(waf1/cip1) was dispensable, since p21 antisense did not modify cell cycle arrest. On the other hand, NaB-induced apoptosis was abolished by p21 antisense or p21PCNA-. In addition, NaB decreased PCNA levels, but increased the association of PCNA with P21(waf1/cip1). These results suggested that NaB-induced apoptosis required P21(waf1/cip1) and its interaction with PCNA.