Genomics Division, Department of Agricultural Bio-Resources, National Institute of Agricultural Sciences, Rural Development Administration, Wansan-gu, Jeonju 54874, Korea.
Molecules. 2018 Nov 15;23(11):2983. doi: 10.3390/molecules23112983.
Glucosinolates (GSL) are naturally occurring β-d-thioglucosides found across the cruciferous vegetables. Core structure formation and side-chain modifications lead to the synthesis of more than 200 types of GSLs in Brassicaceae. Isothiocyanates (ITCs) are chemoprotectives produced as the hydrolyzed product of GSLs by enzyme myrosinase. Benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC) and sulforaphane ([1-isothioyanato-4-(methyl-sulfinyl) butane], SFN) are potential ITCs with efficient therapeutic properties. Beneficial role of BITC, PEITC and SFN was widely studied against various cancers such as breast, brain, blood, bone, colon, gastric, liver, lung, oral, pancreatic, prostate and so forth. Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor limits the tumor progression. Induction of ARE (antioxidant responsive element) and ROS (reactive oxygen species) mediated pathway by Nrf2 controls the activity of nuclear factor-kappaB (NF-κB). NF-κB has a double edged role in the immune system. NF-κB induced during inflammatory is essential for an acute immune process. Meanwhile, hyper activation of NF-κB transcription factors was witnessed in the tumor cells. Antagonistic activity of BITC, PEITC and SFN against cancer was related with the direct/indirect interaction with Nrf2 and NF-κB protein. All three ITCs able to disrupts Nrf2-Keap1 complex and translocate Nrf2 into the nucleus. BITC have the affinity to inhibit the NF-κB than SFN due to the presence of additional benzyl structure. This review will give the overview on chemo preventive of ITCs against several types of cancer cell lines. We have also discussed the molecular interaction(s) of the antagonistic effect of BITC, PEITC and SFN with Nrf2 and NF-κB to prevent cancer.
硫代葡萄糖苷(GSL)是十字花科蔬菜中天然存在的β-D-硫代葡萄糖苷。核心结构的形成和侧链修饰导致在芸薹属植物中合成了 200 多种 GSL。异硫氰酸酯(ITC)是 GSL 经酶芥子酶水解产生的化学保护剂。苄基异硫氰酸酯(BITC)、苯乙基异硫氰酸酯(PEITC)和萝卜硫素([1-异硫氰酸基-4-(甲基亚磺酰基)丁烷],SFN)是具有有效治疗特性的潜在 ITC。BITC、PEITC 和 SFN 的有益作用已广泛研究用于治疗各种癌症,如乳腺癌、脑癌、血液癌、骨癌、结肠癌、胃癌、肝癌、肺癌、口腔癌、胰腺癌、前列腺癌等。核因子红细胞 2 相关因子 2(Nrf2)是一种关键的转录因子,限制肿瘤的进展。Nrf2 诱导 ARE(抗氧化反应元件)和 ROS(活性氧)介导的途径控制核因子-κB(NF-κB)的活性。NF-κB 在免疫系统中具有双重作用。在炎症过程中诱导的 NF-κB 对于急性免疫过程至关重要。同时,在肿瘤细胞中观察到 NF-κB 转录因子的过度激活。BITC、PEITC 和 SFN 对癌症的拮抗活性与 Nrf2 和 NF-κB 蛋白的直接/间接相互作用有关。三种 ITC 都能够破坏 Nrf2-Keap1 复合物并将 Nrf2 转位到细胞核中。由于存在额外的苄基结构,BITC 比 SFN 更能抑制 NF-κB。本综述将概述 ITC 对几种类型的癌细胞系的化学预防作用。我们还讨论了 BITC、PEITC 和 SFN 与 Nrf2 和 NF-κB 的拮抗作用的分子相互作用,以预防癌症。