Tang Li, Zhang Yuesheng, Jobson Hillary E, Li Jun, Stephenson Katherine K, Wade Kristina L, Fahey Jed W
Department of Chemoprevention, Roswell Park Cancer Institute, Elm and Carlton Streets, Science 711, Buffalo, NY 14263, USA.
Mol Cancer Ther. 2006 Apr;5(4):935-44. doi: 10.1158/1535-7163.MCT-05-0476.
We have previously shown that broccoli sprouts are a rich source of chemopreventive isothiocyanates, which potently induce carcinogen-detoxifying enzymes and inhibit the development of mammary and skin tumors in rodents. However, the principal isothiocyanate present in broccoli sprout extracts, sulforaphane, not only induces carcinogen-detoxifying enzymes but also activates apoptosis and blocks cell cycle progression. In this article, we show that an aqueous extract of broccoli sprouts potently inhibits the growth of human bladder carcinoma cells in culture and that this inhibition is almost exclusively due to the isothiocyanates. Isothiocyanates are present in broccoli sprouts as their glucosinolate precursors and blocking their conversion to isothiocyanates abolishes the antiproliferative activity of the extract. Moreover, the potency of isothiocyanates in the extract in inhibiting cancer cell growth was almost identical to that of synthetic sulforaphane, as judged by their IC50 values (6.6 versus 6.8 micromol/L), suggesting that other isothiocyanates in the extract may be biologically similar to sulforaphane and that nonisothiocyanate substances in the extract may not interfere with the antiproliferative activity of the isothiocyanates. Further study showed that the isothiocyanate extract of broccoli sprouts activated the mitochondria-mediated apoptosis pathway and halted cells in S and M phases. Cell cycle arrest was associated with down-regulation of Cdc25C and disruption of mitotic spindles. These data show that broccoli sprout isothiocyanate extract is a highly promising substance for cancer prevention/treatment and that its antiproliferative activity is exclusively derived from isothiocyanates.
我们之前已经表明，西兰花芽是化学预防异硫氰酸盐的丰富来源，这些异硫氰酸盐能有效诱导致癌物解毒酶，并抑制啮齿动物乳腺和皮肤肿瘤的发展。然而，西兰花芽提取物中存在的主要异硫氰酸盐——萝卜硫素，不仅能诱导致癌物解毒酶，还能激活细胞凋亡并阻断细胞周期进程。在本文中，我们表明西兰花芽的水提取物能有效抑制培养的人膀胱癌细胞的生长，并且这种抑制几乎完全归因于异硫氰酸盐。异硫氰酸盐在西兰花芽中以其硫代葡萄糖苷前体的形式存在，阻断它们向异硫氰酸盐的转化会消除提取物的抗增殖活性。此外，通过IC50值（6.6对6.8微摩尔/升）判断，提取物中异硫氰酸盐抑制癌细胞生长的效力与合成萝卜硫素几乎相同，这表明提取物中的其他异硫氰酸盐在生物学上可能与萝卜硫素相似，并且提取物中的非异硫氰酸盐物质可能不会干扰异硫氰酸盐的抗增殖活性。进一步的研究表明，西兰花芽的异硫氰酸盐提取物激活了线粒体介导的细胞凋亡途径，并使细胞停滞在S期和M期。细胞周期停滞与Cdc25C的下调和有丝分裂纺锤体的破坏有关。这些数据表明，西兰花芽异硫氰酸盐提取物是一种极有前景的癌症预防/治疗物质，其抗增殖活性完全源自异硫氰酸盐。
