UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, Malaysia.
CREA Consiglio per la ricerca in agricoltura e l'analisi dell'economia agraria, Centro di Ricerca Agricoltura e Ambiente (CREA-AA), 40128 Bologna, Italy.
Molecules. 2020 Mar 9;25(5):1240. doi: 10.3390/molecules25051240.
Gluconasturtiin, a glucosinolate present in watercress, is hydrolysed by myrosinase to form gluconasturtiin-isothiocyanate (GNST-ITC), which has potential chemopreventive effects; however, the underlying mechanisms of action have not been explored, mainly in human cell lines. The purpose of the study is to evaluate the cytotoxicity of GNST-ITC and to further assess its potential to induce apoptosis. GNST-ITC inhibited cell proliferation in both human hepatocarcinoma (HepG2) and human breast adenocarcinoma (MCF-7) cells with IC values of 7.83 µM and 5.02 µM, respectively. Morphological changes as a result of GNST-ITC-induced apoptosis showed chromatin condensation, nuclear fragmentation, and membrane blebbing. Additionally, Annexin V assay showed proportion of cells in early and late apoptosis upon exposure to GNST-ITC in a time-dependent manner. To delineate the mechanism of apoptosis, cell cycle arrest and expression of caspases were studied. GNST-ITC induced a time-dependent G/M phase arrest, with reduction of 82% and 93% in HepG2 and MCF-7 cell lines, respectively. The same treatment also led to the subsequent expression of caspase-3/7 and -9 in both cells demonstrating mitochondrial-associated cell death. Collectively, these results reveal that GNST-ITC can inhibit cell proliferation and can induce cell death in HepG2 and MCF-7 cancer cells via apoptosis, highlighting its potential development as an anticancer agent.
葡萄糖冬斯丁，一种存在于西洋菜中的硫代葡萄糖苷，被黑芥子酶水解形成葡萄糖冬斯丁异硫氰酸盐（GNST-ITC），具有潜在的化学预防作用；然而，其作用机制尚未得到探索，主要在人细胞系中。本研究旨在评估 GNST-ITC 的细胞毒性，并进一步评估其诱导细胞凋亡的潜力。GNST-ITC 对人肝癌（HepG2）和人乳腺癌（MCF-7）细胞的增殖均具有抑制作用，IC 值分别为 7.83 µM 和 5.02 µM。GNST-ITC 诱导的细胞凋亡导致染色质浓缩、核片段化和细胞膜起泡等形态学变化。此外，Annexin V 检测显示，随着 GNST-ITC 暴露时间的延长，早期和晚期凋亡的细胞比例呈时间依赖性增加。为了阐明凋亡的机制，研究了细胞周期停滞和半胱天冬酶的表达。GNST-ITC 诱导了时间依赖性的 G/M 期阻滞，分别使 HepG2 和 MCF-7 细胞系的阻滞率降低了 82%和 93%。同样的处理也导致了随后在两种细胞中 caspase-3/7 和 -9 的表达，表明线粒体相关的细胞死亡。综上所述，这些结果表明，GNST-ITC 可以通过凋亡抑制 HepG2 和 MCF-7 癌细胞的增殖，并诱导其死亡，提示其作为抗癌剂的潜在开发价值。
