萝卜硫素干扰微管与线粒体动力学抗肿瘤机制

doi:10.3969/j.issn.1006-7795.2023.03.001

摘要/Abstract

摘要： 萝卜硫素及其代谢物（sulforaphanes, SFNs）是源于十字花科植物，诸如西兰花、甘蓝、红萝卜的天然活性物质。SFNs主要代谢物是萝卜硫素-N-乙酰半胱氨酸（SFN N-acetylcysteine，SFN-NAC）、萝卜硫素半胱氨酸（SFN cysteine，SFN-Cys）和萝卜硫素谷胱甘肽（SFN glutathione，SFN-GSH）等。萝卜硫素可抑制多种肿瘤细胞生长，对正常组织毒性较低,但其在循环中的半衰期仅为2 h。然而，SFN-NAC和 SFN-Cys在循环中的半衰期较长，给小鼠注射SFN后，SFN-NAC和 SFN-Cys 72 h才经尿液排泄干净。十多年来笔者对SFNs的抑癌机制进行了系统地研究，除了半衰期不同外，几种SFNs的抑癌机制高度一致。笔者发现SFNs是一类微管抑制剂，通过干扰微管的结构，调节微管动力学平衡，以及抑制线粒体功能导致肿瘤细胞生长抑制和凋亡。

关键词: 萝卜硫素, 微管, 自噬, 凋亡, 蛋白质稳态

Abstract: Sulforaphanes (SFNs) are naturally active substances extracted from cruciferous plants such as broccoli, cabbage, and carrot. SFNs metabolize to produce sulforaphane N-acetylcysteine (SFN-NAC), sulforaphane cysteine (SFN-Cys) and sulforaphane glutathione (SFN-GSH). Sulforaphane inhibits the growth of many tumor cells and has low toxicity to normal tissues, but its circulating half-life is only 2 h. However, either SFN-NAC or SFN-Cys has a longer half-life in circulation. After injected into mice, SFN-NAC and SFN-Cys are excreted through urine after 72 h. For more than ten years, we have systematically studied the anti-cancer mechanisms of SFN and their metabolites (SFNs). Except for their different half-lives, the anti-cancer mechanisms of SFNs are highly consistent. We found that SFNs are a class of microtubule inhibitors that cause tumor cell growth inhibition and apoptosis by interfering with the structure of microtubules, regulating microtubule dynamic balance, and inhibiting mitochondrial function.

Key words: sulforaphane, microtubule, autophagy, apoptosis, protein homeostasis

中图分类号:

周妍, 吴巍. 萝卜硫素干扰微管与线粒体动力学抗肿瘤机制[J]. 首都医科大学学报, 2023, 44(3): 363-369.

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