Apigenin induces cell cycle arrest and p21/WAF1 expression in a p53-independent pathway.
Apigenin induces cell cycle arrest and p21/WAF1 expression in a p53-independent pathway.
复制标题
DOI：
10.3892/ijo.26.1.185
复制
发表时间：
2005
影响因子：
5.2
通讯作者：
Nobumasa Takagaki;Y. Sowa;Teruki Oki;Ryoko Nakanishi;Shingo Yogosawa;T. Sakai
中科院分区：
文献类型：
--
作者：
Nobumasa Takagaki;Y. Sowa;Teruki Oki;Ryoko Nakanishi;Shingo Yogosawa;T. Sakai
芹菜素是一种常见的膳食类黄酮，已被证明在许多癌细胞系中诱导细胞生长抑制和细胞周期停滞。芹菜素的一个重要作用是增加正常细胞中肿瘤抑制因子p53的稳定性。因此，芹菜素有望通过改变p53蛋白的作用在癌症预防中发挥重要作用。然而，芹菜素对p53突变癌细胞的作用机制尚未被揭示。我们评估了芹菜素对p53突变细胞系细胞生长和细胞周期的影响。芹菜素治疗导致生长抑制和G2/M期阻滞在两个p53突变的癌细胞系，HT-29和MG 63。这些作用与p21/WAF 1蛋白表达的显著增加有关。我们已经表明，p21/WAF 1 mRNA的表达也显着增加与芹菜素的剂量和时间依赖性的方式处理。然而，我们不能检测p21/WAF 1启动子活性与芹菜素处理后。类似地，来自pG 13-Luc（p53应答启动子质粒）的启动子活性不被用芹菜素处理（有或没有p53蛋白表达）激活。这些结果表明，在p53突变的细胞系中，芹菜素存在p53非依赖性途径，其诱导p21/WAF 1表达和生长抑制。芹菜素不仅可以作为野生型p53状态的化学预防剂，而且可以作为突变型p53癌症的化学预防剂。
Apigenin, a common dietary flavonoid, has been shown to induce cell growth-inhibition and cell cycle arrest in many cancer cell lines. One important effect of apigenin is to increase the stability of the tumor suppressor p53 in normal cells. Therefore, apigenin is expected to play a large role in cancer prevention by modifying the effects of p53 protein. However, the mechanisms of apigenin's effects on p53-mutant cancer cells have not been revealed yet. We assessed the influence of apigenin on cell growth and the cell cycle in p53-mutant cell lines. Treatment with apigenin resulted in growth-inhibition and G2/M phase arrest in two p53-mutant cancer cell lines, HT-29 and MG63. These effects were associated with a marked increase in the protein expression of p21/WAF1. We have shown that p21/WAF1 mRNA expression was also markedly increased by treatment with apigenin in a dose- and time-dependent manner. However, we could not detect p21/WAF1 promoter activity following treatment with apigenin. Similarly, promoter activity from pG13-Luc, a p53-responsive promoter plasmid, was not activated by treatment with apigenin with or without p53 protein expression. These results suggest that there is a p53-independent pathway for apigenin in p53-mutant cell lines, which induces p21/WAF1 expression and growth-inhibition. Apigenin may be a useful chemopreventive agent not only in wild-type p53 status, but also in cancer with mutant p53.