Inhibition of urinary bladder carcinogenesis by broccoli sprouts
Inhibition of urinary bladder carcinogenesis by broccoli sprouts
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DOI：
10.1158/0008-5472.can-07-5009
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发表时间：
2008-03-01
期刊：
影响因子：
11.2
通讯作者：
Zhang, Yuesheng
中科院分区：
文献类型：
--
作者：
Munday, Rex;Mhawech-Fauceglia, Paulette;Zhang, Yuesheng
异硫氰酸盐是一类众所周知的癌症化学预防剂，西兰花芽是多种异硫氰酸盐的丰富来源。我们在此报道，通过饮食向大鼠施用西兰花芽的冻干水提取物，显着且剂量依赖性地抑制由N-丁基-N-(4-羟丁基)亚硝胺诱导的膀胱癌的发展。膀胱癌的发病率、多样性、大小和进展均受到提取物的抑制，而提取物本身不会引起膀胱的组织学变化。此外，提取物对膀胱癌发生的抑制作用与膀胱中谷胱甘肽S-转移酶和NAD(P)H:醌氧化还原酶I的显着诱导有关，这些酶是对抗氧化剂和致癌物的重要保护剂。异硫氰酸盐在体内代谢为二硫代氨基甲酸盐，但二硫代氨基甲酸盐很容易解离为异硫氰酸盐。我们发现，提取物中 >70% 的异硫氰酸盐在单次口服后 12 小时内以异硫氰酸盐当量（异硫氰酸盐 + 二硫代氨基甲酸盐）的形式从尿液中排出。剂量，表明生物利用度高且尿排泄快。此外，经提取物处理的大鼠尿液中异硫氰酸盐当量的浓度比血浆中的异硫氰酸盐当量浓度高2至3个数量级，表明膀胱上皮（膀胱癌发展的主要部位）最容易暴露于口服。给予异硫氰酸盐。事实上，膀胱中异硫氰酸盐当量的组织水平显着高于肝脏中的水平。总之，西兰花芽提取物是一种非常有前途的预防膀胱癌的物质，提取物中的异硫氰酸盐通过尿液选择性地输送到膀胱上皮。
Isothiocyanates are a well-known class of cancer chemopreventive agents, and broccoli sprouts are a rich source of several isothiocyanates. We report herein that dietary administration to rats of a freeze-dried aqueous extract of broccoli sprouts significantly and dose-dependently inhibited bladder cancer development induced by N-butyl-N-(4-hydroxybutyl) nitrosamine. The incidence, multiplicity, size, and progression of bladder cancer were all inhibited by the extract, while the extract itself caused no histologic changes in the bladder. Moreover, inhibition of bladder carcinogenesis by the extract was associated with significant induction of glutathione S-transferase and NAD(P)H:quinone oxidoreductase I in the bladder, enzymes that are important protectants against oxidants and carcinogens. Isothiocyanates are metabolized to dithiocarbamates in vivo, but dithiocarbamates readily dissociate to isothiocyanates. We found that >70% of the isothincyanates present in the extract were excreted in the urine as isothiocyanate equivalents (isothiocyanates + dithiocarbamates) in 12 h after a single p.o. dose, indicating high bioavailability and rapid urinary excretion. In addition, the concentrations of isothiocyanate equivalents in the urine of extract-treated rats were 2 to 3 orders of magnitude higher than those in plasma, indicating that the bladder epithelium, the major site of bladder cancer development, is most exposed to p.o. dosed isothiocyanate. Indeed, tissue levels of isothiocyanate equivalents in the bladder were significantly higher than in the liver. In conclusion, broccoli sprout extract is a highly promising substance for bladder cancer prevention and the isothiocyanates in the extract are selectively delivered to the bladder epithelium through urinary excretion.