Indole3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells
Indole3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells
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DOI：
10.1038/sj.onc.1204365
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发表时间：
2001-05-24
期刊：
影响因子：
8
通讯作者：
Sarkar, FH
中科院分区：
文献类型：
--
作者：
Chinni, SR;Li, YW;Sarkar, FH
前列腺癌是男性最常见的癌症之一，是美国男性癌症相关死亡的第二大原因。最近的饮食和流行病学研究表明，饮食中摄入水果和蔬菜有助于降低前列腺癌的发病率。富含水果和蔬菜的饮食提供了植物化学物质，特别是吲哚-3-甲醇(I3C)，它可能对预防许多类型的癌症负责，包括与激素相关的癌症，如前列腺癌。然而，关于I3C在前列腺癌中的作用和分子机制(S)的研究还没有进行。在本研究中，我们研究了I3C是否对前列腺癌细胞有任何作用，如果是，我们试图确定I3C对前列腺癌细胞产生生物学效应的潜在分子机制(S)。在这里，我们首次报道了I3C抑制PC-3前列腺癌细胞的生长。I3C还诱导PC-3细胞周期停滞于G1期，这可能与I3C上调p21(WAF1)和p27(Klp1)CDK抑制剂，进而与细胞周期蛋白D1和E相关，下调CDK6蛋白激酶水平和活性有关。P21(WAF1)的诱导似乎是转录上调的，并且不依赖于P53反应元件。此外，I3C还抑制PC-3细胞中视网膜母细胞瘤(Rb)蛋白的高磷酸化。用DNA梯状条带和多聚(ADP-核糖)聚合酶(PARP)裂解的方法，观察到当I3C处理时，该细胞系也被诱导了凋亡。我们还发现，在I3C处理的细胞中，Bax表达上调，而Bcl2表达下调。这些作用也可能是通过在I3C处理的PC-3细胞中观察到的核因子-kappaB的下调而起作用的。这些结果表明，I3C通过诱导细胞周期停滞于G1期，导致细胞凋亡，从而抑制PC-3前列腺癌的生长，并调节细胞凋亡相关基因的表达。这些发现表明，I3C可能是一种有效的前列腺癌化学预防或治疗药物！癌症。致癌基因(2001)20,2927-2936。
Prostate cancer is one of the most common cancers in men and it is the second leading cause of cancer related death in men in the United States. Recent dietary and epidemiological studies have suggested the benefit of dietary intake of fruits and vegetables in lowering the incidence of prostate cancer. A diet rich in fruits and vegetables provides phytochemicals, particularly indole-3-carbinol (I3C), which may be responsible for the prevention of many types of cancer, including hormone-related cancers such as prostate. Studies to elucidate the role and the molecular mechanism(s) of action of I3C in prostate cancer, however, have not been conducted. In the current study, we investigated whether I3C had any effect against prostate cancer cells and, if so, attempts were made to identify the potential molecular mechanism(s) by which I3C elicits its biological effects on prostate cancer cells. Here we report for the first time that I3C inhibits the growth of PC-3 prostate cancer cells. Induction of G1 cell cycle arrest was also observed in PC-3 cells treated with I3C, which may be due to the observed effects of I3C in the up-regulation of p21(WAF1) and p27(Klp1) CDK inhibitors, followed by their association with cyclin D1 and E and down-regulation of CDK6 protein kinase levels and activity. The induction of p21(WAF1) appears to be transcriptionally upregulated and independent of the p53 responsive element. In addition, I3C inhibited the hyperpohosphorylation of the Retinoblastoma (Rb) protein in PC-3 cells. Induction of apoptosis was also observed in this cell line when treated with I3C, as measured by DNA laddering and poly (ADP-ribose) polymersae (PARP) cleavage. We also found an up-regulation of Bax, and down-regulation of Bcl-2 in I3C-treated cells. These effects may also be mediated by the down-regulation of NF-kappaB observed in I3C treated PC-3 cells. From these results, we conclude that I3C inhibits the growth of PC-3 prostate cancer cells by inducing G1 cell cycle arrest leading to apoptosis, and regulates the expression of apoptosis-related genes. These findings suggest that I3C may be an effective chemopreventive or therapeutic agent against prostate! cancer. Oncogene (2001) 20, 2927-2936.