萝卜硫素干扰微管与线粒体动力学抗肿瘤机制

A view of sulforaphane interference with microtubules and mitochondrial kinetics in anti-cancer mechanisms

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。

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.