Allyl isothiocyanate-rich mustard seed powder inhibits bladder cancer growth and muscle invasion
Allyl isothiocyanate-rich mustard seed powder inhibits bladder cancer growth and muscle invasion
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DOI：
10.1093/carcin/bgq202
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发表时间：
2010-12-01
期刊：
影响因子：
4.7
通讯作者：
Zhang, Yuesheng
中科院分区：
文献类型：
--
作者：
Bhattacharya, Arup;Li, Yun;Zhang, Yuesheng
异硫氰酸烯丙酯（AITC），它存在于许多常见的十字花科蔬菜，最近被证明是选择性地通过尿液排泄到膀胱癌组织，并抑制膀胱癌的发展在大鼠。本研究旨在验证含有AITC的十字花科蔬菜也抑制膀胱癌发展的假设。我们专注于富含AITC的芥菜籽粉（MSP-1）。AITC作为其硫代葡萄糖苷前体（芥子苷）稳定储存在MSP-1中。然而，在加入水后，黑芥子苷很容易被伴随的内源黑芥子酶水解。黑芥子酶也是芥子苷在体内完全转化为AITC所必需的，但MSP-1的基质对AITC的生物利用度没有影响。Sinigrin本身没有生物活性，而水合MSP-1在体外引起膀胱癌细胞系的凋亡和G（2）/M期阻滞。水合MSP-1和添加黑芥子酶的纯黑芥子苷之间的比较表明，MSP-1的抗癌作用主要（如果不是完全）来自由黑芥子苷产生的AITC。在原位大鼠膀胱癌模型中，口服MSP-1 71.5 mg/kg（芥子苷剂量为9 μ mol/kg）抑制膀胱癌生长34.5%（P < 0.05），并100%阻断肌肉侵袭。此外，抗癌活性与关键癌症治疗靶点的显著调节相关，包括血管内皮生长因子、细胞周期蛋白B1和半胱天冬酶3。在等摩尔的基础上，作为MSP-1递送的AITC的抗癌活性似乎比纯AITC的抗癌活性更强。因此，MSP-1是AITC的有吸引力的递送载体，并且它强烈抑制膀胱癌的发展和进展。
Allyl isothiocyanate (AITC), which occurs in many common cruciferous vegetables, was recently shown to be selectively delivered to bladder cancer tissues through urinary excretion and to inhibit bladder cancer development in rats. The present investigation was designed to test the hypothesis that AITC-containing cruciferous vegetables also inhibit bladder cancer development. We focused on an AITC-rich mustard seed powder (MSP-1). AITC was stably stored as its glucosinolate precursor (sinigrin) in MSP-1. Upon addition of water, however, sinigrin was readily hydrolyzed by the accompanying endogenous myrosinase. This myrosinase was also required for full conversion of sinigrin to AITC in vivo, but the matrix of MSP-1 had no effect on AITC bioavailability. Sinigrin itself was not bioactive, whereas hydrated MSP-1 caused apoptosis and G(2)/M phase arrest in bladder cancer cell lines in vitro. Comparison between hydrated MSP-1 and pure sinigrin with added myrosinase suggested that the anticancer effect of MSP-1 was derived principally, if not entirely, from the AITC generated from sinigrin. In an orthotopic rat bladder cancer model, oral MSP-1 at 71.5 mg/kg (sinigrin dose of 9 mu mol/kg) inhibited bladder cancer growth by 34.5% (P < 0.05) and blocked muscle invasion by 100%. Moreover, the anticancer activity was associated with significant modulation of key cancer therapeutic targets, including vascular endothelial growth factor, cyclin B1 and caspase 3. On an equimolar basis, the anticancer activity of AITC delivered as MSP-1 appears to be more robust than that of pure AITC. MSP-1 is thus an attractive delivery vehicle for AITC and it strongly inhibits bladder cancer development and progression.