Department of Molecular biology and Human genetics, Tzu Chi University, Hualien, Taiwan.
Institute of Medical Science, Tzu Chi University, Hualien, Taiwan.
Food Funct. 2020 Oct 21;11(10):9010-9019. doi: 10.1039/d0fo01565b.
Cruciferous vegetables are good sources of phytochemicals that have the potential to prevent cancer. Benzyl isothiocyanate (BITC) is the hydrolysis product of glucosinolates that are especially abundant in cruciferous vegetables. The anti-cancer activities of BITC have been studied for decades. The mechanisms of reducing the incidence of cancer by BITC involve multiple pathways, including the inhibition of proliferation, induction of apoptosis and inhibition of angiogenesis. One of the major common phenotypes induced by BITC in previous studies is G2/M cell cycle arrest. Therefore, interference of mitosis progression is likely to be an important anti-tumor mechanism of BITC. Using immunofluorescence staining, we show that BITC induces cell arrest in mitosis by perturbation of mitotic spindles. The abnormal mitotic spindles were resulted from the inactivation of Aurora A by BITC. The fact that BITC inhibits the activation of Aurora A and disrupts mitotic spindles provides one of the possible explanations why BITC is able to arrest cells in the G2/M phase and induce apoptosis in many previous studies. Besides, Aurora A is an essential player of mitosis and also has non-mitotic functions in tumorigenesis. As an inhibitor of Aurora A, BITC not only is an antimitotic agent but also inhibits tumor progression via many pathways.
十字花科蔬菜是植物化学物质的良好来源,这些物质具有预防癌症的潜力。苄基异硫氰酸酯(BITC)是硫代葡萄糖苷的水解产物,尤其在十字花科蔬菜中含量丰富。BITC 的抗癌活性已经研究了几十年。BITC 通过多种途径减少癌症发病率,包括抑制增殖、诱导细胞凋亡和抑制血管生成。在之前的研究中,BITC 诱导的主要共同表型之一是 G2/M 细胞周期停滞。因此,干扰有丝分裂进程可能是 BITC 的重要抗肿瘤机制。通过免疫荧光染色,我们表明 BITC 通过干扰有丝分裂纺锤体诱导细胞有丝分裂停滞。异常的有丝分裂纺锤体是由于 BITC 使 Aurora A 失活所致。BITC 抑制 Aurora A 的激活并破坏有丝分裂纺锤体,这一事实为 BITC 能够使细胞在 G2/M 期停滞并在许多先前的研究中诱导细胞凋亡提供了一种可能的解释。此外,Aurora A 是有丝分裂的必需因子,在肿瘤发生中也具有非有丝分裂功能。作为 Aurora A 的抑制剂,BITC 不仅是一种抗有丝分裂剂,而且还通过多种途径抑制肿瘤进展。