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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Mutant p53 mediated induction of cell cycle arrest and apoptosis at G1 phase by 9-hydroxyellipticine.
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Mutant p53 mediated induction of cell cycle arrest and apoptosis at G1 phase by 9-hydroxyellipticine.

机译：突变的p53介导9-羟基玫瑰树碱诱导G1期细胞周期停滞和凋亡。

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摘要

Wild-type p53 causes cell-cycle arrest at late G1 phase and induction of apoptosis by up- regulation of waf1 and bax, respectively. Although in many cancer cells p53 is frequently mutated and loses its functions, we have proposed that mutant p53 may be involved in the anticancer mechanism of 9-hydroxy ellipticine (9HE). It was shown using flow cytometry that 9HE (10 microM) caused induction of apoptosis in G1 phase of the cell cycle in mutant p53 (p53ala143, p53his175, orp53his273) transfected Saos-2 cells, but not in p53-deficient parental Saos-2 cells. Similar induction of apoptosis was observed 24-48 h after treatment with 9HE in mutant p53-containing SW480, SK-BR-3 and MKN-1, but not in p53-deficient KATO m cells. Using G1 phase cells isolated by centrifugal elutriation, it was confirmed that 9HE caused cell cycle arrest at G1 phase and subsequently induced G1 phase-restricted apoptosis. In accordance with the induction of arrest and apoptosis in G1 phase, 9HE caused up-regulation of waf1 and bax mRNA in mutant p53-containing cells, but not in p53-deficient parental Saos-2 cells. In control experiments, adriamycin (ADR) showed neither G1-restricted apoptosis nor elevation of bax mRNA. It is suggested that 9HE may cause G1 arrest and induction of G1 phase-restricted apoptosis by restoring the wild-type function of mutant p53 protein.
机译：野生型p53分别通过上调waf1和bax导致细胞周期停滞在G1期晚期并诱导凋亡。尽管在许多癌细胞中，p53经常发生突变并丧失其功能，但我们已经提出，突变体p53可能参与9-羟基玫瑰树碱（9HE）的抗癌机制。使用流式细胞仪显示，9HE（10 microM）在突变的p53（p53ala143，p53his175，orp53his273）转染的Saos-2细胞中诱导了细胞周期G1期的凋亡，但在缺乏p53的亲本Saos-2细胞中却没有诱导。 。 9HE处理后24-48小时，在含有突变体p53的SW480，SK-BR-3和MKN-1中观察到了类似的凋亡诱导，但在缺乏p53的KATO m细胞中没有观察到。使用通过离心淘析分离的G1期细胞，证实了9HE引起细胞周期停滞在G1期并随后诱导了G1期限制的凋亡。与诱导G1期阻滞和凋亡有关，9HE在含突变p53的细胞中引起了waf1和bax mRNA的上调，而在缺乏p53的亲本Saos-2细胞中则没有。在对照实验中，阿霉素（ADR）既不显示G1限制的凋亡也不显示bax mRNA的升高。提示9HE可能通过恢复突变型p53蛋白的野生型功能而引起G1停滞并诱导G1期限制性凋亡。

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