Inhibition of bladder cancer by broccoli isothiocyanates sulforaphane and erucin: characterization, metabolism, and interconversion.
Inhibition of bladder cancer by broccoli isothiocyanates sulforaphane and erucin: characterization, metabolism, and interconversion.
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DOI：
10.1002/mnfr.201200276
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发表时间：
2012-11
影响因子：
5.2
通讯作者：
Mortazavi, Amir
中科院分区：
文献类型：
--
作者：
Abbaoui, Besma;Riedl, Kenneth M.;Ralston, Robin A.;Thomas-Ahner, Jennifer M.;Schwartz, Steven J.;Clinton, Steven K.;Mortazavi, Amir
流行病学证据表明，富含十字花科蔬菜（尤其是西兰花）的饮食与较低的膀胱癌风险相关。我们的目标是研究这些观察结果并确定异硫氰酸盐在一级或二级膀胱癌预防中的作用。我们最初研究西兰花和西兰花芽提取物和纯异硫氰酸盐抑制正常、非侵入性 (RT4) 和侵入性 (J82、UMUC3) 人类尿路上皮细胞活力的机制。萝卜硫素 (IC50= 5.66±1.2μM) 和芥酸 (IC50= 8.79±1.3μM) 被发现是最有效的抑制剂，而正常细胞最不敏感。这一观察结果与生存素、EGFR 和 HER2/neu、G2/M 细胞周期积累和细胞凋亡的下调有关。在小鼠 UMUC3 异种移植模型中，我们饲喂含有 4% 西兰花芽或 2% 西兰花芽异硫氰酸酯提取物的半纯化饮食；或灌胃纯萝卜硫素或芥酸（各自浓度为 295 μmol/kg，与饮食暴露相似）；并报告肿瘤重量分别减少了 42% (p=0.02)、42% (p=0.04)、33% (p=0.04) 和 58% (p<0.0001)。萝卜硫素和芥酸代谢物存在于小鼠血浆（微摩尔范围）和肿瘤组织中，其中 N-乙酰半胱氨酸缀合物最丰富。观察到萝卜硫素和芥酸代谢物的相互转化。这项工作支持开发完全表征的新型食品，用于针对膀胱癌预防的 I/II 期人体研究。
Epidemiologic evidence suggests diets rich in cruciferous vegetables, particularly broccoli, are associated with lower bladder cancer risk. Our objectives are to investigate these observations and determine the role of isothiocyanates in primary or secondary bladder cancer prevention. We initially investigate the mechanisms whereby broccoli and broccoli sprout extracts and pure isothiocyanates inhibit normal, non-invasive (RT4) and invasive (J82, UMUC3) human urothelial cell viability. Sulforaphane (IC50= 5.66±1.2μM) and erucin (IC50= 8.79±1.3μM) are found to be the most potent inhibitors and normal cells are least sensitive. This observation is associated with downregulation of survivin, EGFR and HER2/neu, G2/M cell cycle accumulation and apoptosis. In a murine UMUC3 xenograft model, we fed semipurified diets containing 4% broccoli sprouts, or 2% broccoli sprout isothiocyanate extract; or gavaged pure sulforaphane or erucin (each at 295 μmol/kg, similar to dietary exposure); and report tumor weight reduction of 42% (p=0.02), 42% (p=0.04), 33% (p=0.04) and 58% (p<0.0001), respectively. Sulforaphane and erucin metabolites are present in mouse plasma (micromolar range) and tumor tissue, with N-acetyl cysteine conjugates as the most abundant. Interconversion of sulforaphane and erucin metabolites was observed. This work supports development of fully characterized, novel food products for phase I/II human studies targeting bladder cancer prevention.
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影响因子：
158.5
作者：
Michaud, DS;Spiegelman, D;Giovannucci, EL
通讯作者：
Giovannucci, EL
影响因子：
4.1
作者：
Kassahun, K;Davis, M;Baillie, T
通讯作者：
Baillie, T
影响因子：
4.1
作者：
Conaway, CC;Krzeminski, J;Chung, FL
通讯作者：
Chung, FL
影响因子：
6.2
作者：
Bellmunt, J;Hussain, M;Dinney, CP
通讯作者：
Dinney, CP
影响因子：
4.7
作者：
Bhattacharya, Arup;Tang, Li;Zhang, Yuesheng
通讯作者：
Zhang, Yuesheng