Inhibition of bladder cancer development by allyl isothiocyanate
Inhibition of bladder cancer development by allyl isothiocyanate
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DOI：
10.1093/carcin/bgp303
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发表时间：
2010-02-01
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;Tang, Li;Zhang, Yuesheng
膀胱癌是人类常见的恶性肿瘤之一，复发率也很高。非常需要能够抑制膀胱癌发展和复发的药剂。在这里，我们报告了异硫氰酸烯丙酯（AITC），一种常见的十字花科蔬菜的成分，在体外有效地抑制膀胱癌细胞系的增殖[半最大抑制浓度（IC 50）为2.7-3.3 μ M]，这与深刻的G（2）/M阻滞和细胞凋亡有关。相反，AITC对正常人膀胱上皮细胞的毒性明显较低（IC 50为69.4 μ M）。然后在两种大鼠膀胱癌模型（原位模型和皮下模型）中评价AITC。原位模型密切模仿人膀胱癌的发展和复发。我们表明，口服低剂量的AITC（1毫克/公斤）显着抑制原位膀胱癌的发展和肌肉浸润，但对相同动物的相同癌细胞的皮下异种移植物无效。我们发现尿中AITC当量水平比血浆中高2 - 3个数量级，原位癌组织中AITC当量水平也比皮下癌组织中高3个数量级，这解释了这种差异效应。此外，我们表明，AITC是一种多靶向药物对膀胱癌。总之，AITC通过尿液排泄选择性地递送到膀胱癌组织，并有效地抑制膀胱癌的发展和侵袭。
Bladder cancer is one of the common human cancers and also has a very high recurrence rate. There is a great need for agents capable of inhibiting bladder cancer development and recurrence. Here, we report that allyl isothiocyanate (AITC), an ingredient of many common cruciferous vegetables, potently inhibited the proliferation of bladder carcinoma cell lines in vitro [half maximal inhibitory concentration (IC50) of 2.7-3.3 mu M], which was associated with profound G(2)/M arrest and apoptosis. In contrast, AITC was markedly less toxic to normal human bladder epithelial cells (IC50 of 69.4 mu M). AITC was then evaluated in two rat bladder cancer models in vivo (an orthotopic model and a subcutaneous model). The orthotopic model closely mimics human bladder cancer development and recurrence. We show that a low oral dose of AITC (1 mg/kg) significantly inhibited the development and muscle invasion of the orthotopic bladder cancers but was ineffective against the subcutaneous xenografts of the same cancer cells in the same animals. This differential effect was explained by our finding that urinary levels of AITC equivalent were two to three orders of magnitude higher than that in the plasma and that its levels in the orthotopic cancer tissues were also three orders of magnitude higher than that in the subcutaneous cancer tissues. Moreover, we show that AITC is a multi-targeted agent against bladder cancer. In conclusion, AITC is selectively delivered to bladder cancer tissue through urinary excretion and potently inhibits bladder cancer development and invasion.