Lau Wing-Sze, Chen Tianfeng, Wong Yum-Shing
State Key Laboratory of Agrobiotechnology, Department of Biology, Science Centre, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, P.R. China.
Mol Med Rep. 2010 Nov-Dec;3(6):1023-30. doi: 10.3892/mmr.2010.363. Epub 2010 Sep 15.
Allyl isothiocyanate (AITC) is a constituent of cruciferous vegetables that exhibits antitumor activity. In this study, AITC was shown to inhibit the proliferation of human metastatic colorectal adenocarcinoma SW620 cells in vitro by inducing cell cycle arrest at the G2/M phase. The signaling pathway of AITC action involved the down-regulation of the pivotal Cdc25B and Cdc25C protein phosphatases in the treated cells. Quantitative real-time PCR of AITC-treated SW620 cells revealed a time-dependent down-regulation of Cdc25B and Cdc25C mRNA levels, which resulted in a decrease in the expression levels of these two proteins. Upon prolonged exposure, AITC induced caspase-mediated apoptosis in SW620 cells. The apoptotic process was evidenced by the activation of initiator caspases (-8 and -9) and effector caspases (-3 and -7), and the cleavage of poly(ADP-ribose) polymerase (PARP). The antitumor activity of AITC was further demonstrated in a SW620 xenograft in vivo. Taken together, the results suggest that AITC is a potential candidate for future research in chemoprevention and chemotherapy.
异硫氰酸烯丙酯（AITC）是十字花科蔬菜中的一种成分，具有抗肿瘤活性。在本研究中，AITC被证明可通过诱导细胞周期停滞在G2/M期来抑制人转移性结肠腺癌SW620细胞的体外增殖。AITC作用的信号通路涉及处理后细胞中关键的Cdc25B和Cdc25C蛋白磷酸酶的下调。对AITC处理的SW620细胞进行定量实时PCR显示，Cdc25B和Cdc25C mRNA水平呈时间依赖性下调，导致这两种蛋白的表达水平降低。长时间暴露后，AITC诱导SW620细胞发生半胱天冬酶介导的凋亡。凋亡过程通过起始半胱天冬酶（-8和-9）和效应半胱天冬酶（-3和-7）的激活以及聚（ADP-核糖）聚合酶（PARP）的裂解得以证实。AITC的抗肿瘤活性在体内的SW620异种移植模型中得到进一步证明。综上所述，结果表明AITC是未来化学预防和化疗研究的潜在候选物。
