尽管人们已经知道,食用绿色花椰菜(broccoli)、黄白色花椰菜(cauliflower)、卷心菜等十字花科蔬菜可以预防癌症,但它们具体的抗癌机制却不清楚。
近日,美国加利福尼亚大学圣巴巴拉分校的生化与药理学教授莱斯利·威尔逊(Leslie Wilson)和该校分子细胞与发育生物学系的副教授玛丽·安·乔丹(Mary Ann Jordan)在国际著名学术杂志《癌症发生》(Carcinogenesis)上发表文章,阐明了十字花科蔬菜的抗癌机制。
这篇文章的第一作者、威尔逊教授的研究生奥尔加·阿扎伦科(Olga Azarenko)指出:“在所有癌症中,乳癌的致死率排名第二。但食用十字花科蔬菜(如卷心菜)可预防这种癌症,这是为什么呢?经过我们的研究发现,在这类蔬菜中,含有一种具有预防和抗癌活性的化学物质硫氰酸盐(isothiocyanate)。在绿色和黄白色花椰菜中,这类化学物质的含量是最高的。”
阿扎伦科补充说:“我们的文章主要讨论了硫氰酸盐的抗癌活性。在研究中,这类物质已经表现出较强的抗癌能力,可以降低实验动物的癌症发生率。另外,它们还能抑制人类乳癌细胞的生长,甚至杀死癌细胞。”
阿扎伦科惊奇地发现,硫氰酸盐一直人类癌细胞的方式居然与抗癌药物紫杉醇(taxol)和长春新碱(vincristine)很相似:都是抑制细胞的有丝分裂(对于正常细胞而言,有丝分裂是细胞分裂的重要过程。在这一过程中,染色体会进行复制并准确分配到两个子细胞中)。
在有丝分裂阶段,细胞内会有大量微小的管状物质(即微管,microtubule),它们将帮助细胞把两套染色体分开(一套是原来的,另一套是复制形成的)。与很多来自于其他植物的抗癌物质类似,硫氰酸盐也是抑制干扰微管的功能,从而阻止有丝分裂的正常进行。与其他抗癌药物相比,硫氰酸盐的毒性更低。
威尔逊教授说:“硫氰酸盐可能是一种很有效的癌症预防药物,因为它能阻止癌细胞增殖,并杀死癌变细胞。”此外,硫氰酸盐还可与紫杉醇等抗癌药物联用,以增强抗癌效果,而且不会加重药物毒性。(生物谷Bioon.com)
生物谷推荐原始出处:
Carcinogenesis 2008 29(12):2360-2368; doi:10.1093/carcin/bgn241
Suppression of microtubule dynamic instability and turnover in MCF7 breast cancer cells by sulforaphane
Olga Azarenko, Tatiana Okouneva, Keith W. Singletary1, Mary Ann Jordan and Leslie Wilson*
Department of Molecular, Cellular, and Developmental Biology and the Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA
1 Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL 61801, USA
Sulforaphane (SFN), a prominent isothiocyanate present in cruciferous vegetables, is believed to be responsible along with other isothiocyanates for the cancer preventive activity of such vegetables. SFN arrests mitosis, possibly by affecting spindle microtubule function. A critical property of microtubules is their rapid and time-sensitive growth and shortening dynamics (dynamic instability), and suppression of dynamics by antimitotic anticancer drugs (e.g. taxanes and the vinca alkaloids) is central to the anticancer mechanisms of such drugs. We found that at concentrations that inhibited proliferation and mitosis of MCF7-green fluorescent protein--tubulin breast tumor cells by 50% (15 μM), SFN significantly modified microtubule organization in arrested spindles without modulating the spindle microtubule mass, in a manner similar to that of much more powerful antimitotic drugs. By using quantitative fluorescence video microscopy, we determined that at its mitotic concentration required to inhibit mitosis by 50%, SFN suppressed the dynamic instability of the interphase microtubules in these cells, strongly reducing the rate and extent of growth and shortening and decreasing microtubule turnover, without affecting the polymer mass. SFN suppressed the dynamics of purified microtubules in a similar fashion at concentrations well below those required to depolymerize microtubules, indicating that the suppression of dynamic instability by SFN in cells is due to a direct effect on the microtubules. The results indicate that SFN arrests proliferation and mitosis by stabilizing microtubules in a manner weaker than but similar to more powerful clinically used antimitotic anticancer drugs and strongly support the hypothesis that inhibition of mitosis by microtubule stabilization is important for SFN's chemopreventive activity.