Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells.
Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells.
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发表时间：
2000-03
期刊：
影响因子：
11.2
通讯作者：
L. Gamet-Payrastre;Pengfei Li;S. Lumeau;G. Cassar;M. Dupont;S. Chevolleau;Nicole Gasc;J. Tulliez-J.-Tulli
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作者：
L. Gamet-Payrastre;Pengfei Li;S. Lumeau;G. Cassar;M. Dupont;S. Chevolleau;Nicole Gasc;J. Tulliez-J.-Tulli
萝卜硫素是一种异硫氰酸酯，天然存在于广泛食用的蔬菜中，在西兰花中的浓度特别高。这种化合物已被证明可以阻止大鼠体内化学物质引发的肿瘤形成。虽然萝卜硫素已被提出来调节致癌物质的代谢，但其作用机制仍然知之甚少。我们以前已经证明，萝卜硫素抑制生长的重新启动，并降低静止的人结肠癌细胞（HT 29）的细胞活力。此外，在分化的CaCo 2细胞上观察到的弱作用表明该化合物具有特异性抗癌活性。在这里，我们研究了萝卜硫素对HT 29细胞在其指数生长期的生长和活力的影响。我们观察到萝卜硫素以剂量依赖性方式诱导细胞周期停滞，随后细胞死亡。这种萝卜硫素诱导的细胞周期阻滞与细胞周期蛋白A和B1的表达增加相关。此外，我们清楚地表明，萝卜硫素诱导细胞死亡，通过凋亡过程。事实上，大部分处理的细胞显示出以下特征：（a）磷脂酰丝氨酸从质膜内层易位到外层;（B）典型的染色质浓缩;和（c）与凋亡性细胞死亡相关的超微结构修饰。我们还发现，在萝卜硫素处理的细胞中，p53的表达没有改变。相比之下，而bcl-2未检测到，我们观察到促凋亡蛋白Bax的表达增加，细胞色素c从线粒体释放到胞质溶胶，和聚（ADP-核糖）聚合酶的蛋白水解裂解。总之，我们的研究结果强烈表明，除了解毒酶的激活，诱导细胞凋亡也参与了萝卜硫素相关的化学预防癌症。
Sulforaphane is an isothiocyanate that is present naturally in widely consumed vegetables and has a particularly high concentration in broccoli. This compound has been shown to block the formation of tumors initiated by chemicals in the rat. Although sulforaphane has been proposed to modulate the metabolism of carcinogens, its mechanism of action remains poorly understood. We have previously demonstrated that sulforaphane inhibits the reinitiation of growth and decreases the cellular viability of quiescent human colon carcinoma cells (HT29). Moreover, the weak effect observed on differentiated CaCo2 cells suggests a specific anticancer activity for this compound. Here we investigated the effect of sulforaphane on the growth and viability of HT29 cells during their exponentially growing phase. We observed that sulforaphane induced a cell cycle arrest in a dose-dependent manner, followed by cell death. This sulforaphane-induced cell cycle arrest was correlated with an increased expression of cyclins A and B1. Moreover, we clearly demonstrated that sulforaphane induced cell death via an apoptotic process. Indeed, a large proportion of treated cells display the following: (a) translocation of phosphatidylserine from the inner layer to the outer layer of the plasma membrane; (b) typical chromatin condensation; and (c) ultrastructural modifications related to apoptotic cell death. We also showed that the expression of p53 was not changed in sulforaphane-treated cells. In contrast, whereas bcl-2 was not detected, we observed increased expression of the proapoptotic protein bax, the release of cytochrome c from the mitochondria to the cytosol, and the proteolytic cleavage of poly(ADP-ribose) polymerase. In conclusion, our results strongly suggest that in addition to the activation of detoxifying enzymes, induction of apoptosis is also involved in the sulforaphane-associated chemoprevention of cancer.