Artepillin C in Brazilian propolis induces G0/G1 arrest via stimulation of Cip1/p21 expression in human colon cancer cells
Artepillin C in Brazilian propolis induces G0/G1 arrest via stimulation of Cip1/p21 expression in human colon cancer cells
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DOI：
10.1002/mc.20148
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发表时间：
2005-12-01
影响因子：
4.6
通讯作者：
Kanazawa, K
中科院分区：
文献类型：
--
作者：
Shimizu, K;Das, SK;Kanazawa, K
潜在的化学预防剂存在于食品中。研究了巴西蜂胶中的青蒿素C对结肠癌的影响。我们发现artepillin C是一种生物可利用的抗氧化剂，可以不经任何结合而结合到肠道Caco-2和肝脏HepG2细胞中，并抑制细胞内DNA的氧化。然后将青蒿素C添加到人类结肠癌的WiDr细胞中。剂量依赖性抑制细胞生长，诱导G(0)/G(1)阻滞。这些事件包括细胞周期蛋白D/细胞周期蛋白依赖性激酶4复合物的激酶活性降低，以及视网膜母细胞瘤蛋白Ser 780和807/811磷酸化水平的降低。复合物的抑制剂Cip1/p21和Kip1/p27在蛋白水平上增加。另一方面，Northern blotting显示，artepillin C不影响Kip1/p27 mRNA的表达。用等基因人结直肠癌细胞系进行实验发现，artepillin C在Cip1/p21缺失的HCT116细胞中不能诱导G(0)/G(1)阻滞，而在野生型HCT116细胞中则不能。Artepillin C似乎通过刺激Cip1/p21的表达诱导细胞周期阻滞来预防结肠癌，并且是结肠癌发生中有用的化学预防因子。(c) 2005 Wiley-Liss, Inc。
Potential chemopreventive agents exist in foods. Artepillin C in Brazilian propolis was investigated for its effects on colon carcinogenesis. We had found that artepillin C was a bioavailable antioxidant, which could be incorporated into intestinal Caco-2 and hepatic HepG2 cells without any conjugation and inhibited the oxidation of intracellular DNA. Artepillin C was then added to human colon cancer WiDr cells. It dose-dependently inhibited cell growth, inducing G(0)/G(1) arrest. The events involved a decrease in the kinase activity of a complex of cyclin D/cyclin-dependent kinase 4 and in the levels of retinoblastoma protein phosphorylated at Ser 780 and 807/811. The inhibitors of the complex, Cip1/p21 and Kip1/p27, increased at the protein level. On the other hand, Northern blotting showed that artepillin C did not affect the expression of Kip1/p27 mRNA. According to the experiments using isogenic human colorectal carcinoma cell lines, artepillin C failed to induce G(0)/G(1) arrest in the Cip1/p21-deleted HCT116 cells, but not in the wild-type HCT116 cells. Artepillin C appears to prevent colon cancer through the induction of cell-cycle arrest by stimulating the expression of Cip1/p21 and to be a useful chemopreventing factor in colon carcinogenesis. (c) 2005 Wiley-Liss, Inc.