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萝卜硫素通过诱导谷胱甘肽耗竭和微管解聚来抑制结肠癌衍生肿瘤的生长。

Sulforaphene suppresses growth of colon cancer-derived tumors via induction of glutathione depletion and microtubule depolymerization.

机构信息

Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.

WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seou, Republic of Korea.

出版信息

Mol Nutr Food Res. 2016 May;60(5):1068-78. doi: 10.1002/mnfr.201501011. Epub 2016 Mar 24.

Abstract

SCOPE

Cruciferous vegetables harbor a number of isothiocyanates that have been recognized for their cancer-related properties. Out of these, sulforaphene (a naturally occurring derivative of sulforaphane) has received little attention in studies of colon cancer and its mechanism of action remains to be elucidated.

METHODS AND RESULTS

We observed that sulforaphene inhibited growth of human colon cancer cell lines HCT116, HT-29, KM12, SNU-1040, and DLD-1, while exhibiting negligible toxicity toward nonmalignant cells. Sulforaphene induced G2/M phase cell cycle arrest and apoptosis of colon cancer cells analyzed by flow cytometry, concomitant with phosphorylation of CDK1 and CDC25B at inhibitory sites, and upregulation of the p38 and JNK pathways. It was further determined that sulforaphene is a potent inhibitor of microtubule polymerization while generating reactive oxygen species via the depletion of glutathione. These observations further extended into inhibitory effects against colon tumor growth in a mouse xenograft model.

CONCLUSION

These findings demonstrate that sulforaphene may contribute to the anti-tumor effects of cruciferous vegetables that contain sulforaphene and other isothiocyanates.

摘要

范围

十字花科蔬菜中含有多种异硫氰酸酯,这些物质已因其与癌症相关的特性而受到关注。在这些异硫氰酸酯中,萝卜硫素(硫代葡萄糖苷的天然衍生物)在结肠癌的研究中很少受到关注,其作用机制仍有待阐明。

方法和结果

我们观察到萝卜硫素抑制人结肠癌细胞系 HCT116、HT-29、KM12、SNU-1040 和 DLD-1 的生长,而对非恶性细胞几乎没有毒性。通过流式细胞术分析,萝卜硫素诱导结肠癌细胞的 G2/M 期细胞周期停滞和细胞凋亡,同时抑制 CDK1 和 CDC25B 在抑制性位点的磷酸化,并上调 p38 和 JNK 途径。进一步确定萝卜硫素是微管聚合的有效抑制剂,同时通过谷胱甘肽耗竭产生活性氧。这些观察结果进一步扩展到在小鼠异种移植模型中对结肠肿瘤生长的抑制作用。

结论

这些发现表明,萝卜硫素可能有助于含有萝卜硫素和其他异硫氰酸酯的十字花科蔬菜的抗肿瘤作用。

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