Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98168 Messina, Italy.
IRCCS Centro Neurolesi "Bonino-Pulejo", 98124 Messina, Italy.
Int J Mol Sci. 2019 Apr 19;20(8):1930. doi: 10.3390/ijms20081930.
In the last decades, glucosinolates (GLs), precursors of isothiocyanates (ITCs), have been studied mostly for their chemopreventive and chemotherapeutic properties. The aim of our research was to study the antiproliferative effect of 4-(α-L-rhamnopyranosyloxy) benzyl glucosinolate (glucomoringin; GMG) bioactivated by myrosinase enzyme to form the corresponding isothiocyanate 4-(α-L-rhamnopyranosyloxy) benzyl C (moringin) in SH-SY5Y human neuroblastoma cells. We found that moringin significantly reduced SH-SY5Y cell growth in a time and concentration-dependent ( < 0.05, 0.01, and 0.001 vs. ctrl, after treatment with 16.4 µM moringin for 24, 48, and 72 h, respectively) manner through a mechanism involving the activation of apoptotic machinery. In addition, it altered the normal progression of cells through the cell cycle, increasing the cell population in both G2 and S phases, as well as decreasing that in the G1 phase. Studying the drug mechanism of action, we found that moringin was able to increase the expression of p53, p21, and Bax at both the protein and transcriptional level. Moreover, exposure of SH-SY5Y cells to moringin significantly increased the gene expression of both caspase 3 and 9 and enhanced their cleavage, thereby initiating an intrinsic apoptotic cascade. Finally, moringin inhibited nuclear translocation of NF-κB. Our study demonstrates the ability of moringin to reduce the growth of SH-SY5Y cells and reveals its mechanism of action, suggesting its promising role as an anticancer drug.
在过去的几十年里，芥子油苷（GLs），异硫氰酸酯（ITCs）的前体，主要因其化学预防和化学治疗特性而受到研究。我们研究的目的是研究辣根过氧化物酶酶生物转化 4-（α-L-鼠李吡喃糖氧基）苄基芥子油苷（葡萄糖苷； GMG）形成相应的异硫氰酸 4-（α-L-鼠李吡喃糖氧基）苄基 C（morin）对 SH-SY5Y 人神经母细胞瘤细胞的增殖抑制作用。我们发现，morin 通过激活细胞凋亡机制，以时间和浓度依赖性方式（<0.05、0.01 和 0.001 与对照相比，分别用 16.4 µM morin 处理 24、48 和 72 h 后）显著降低 SH-SY5Y 细胞的生长。此外，它改变了细胞通过细胞周期的正常进程，增加了 G2 和 S 期的细胞群体，同时减少了 G1 期的细胞群体。研究药物作用机制，我们发现 morin 能够在蛋白质和转录水平上增加 p53、p21 和 Bax 的表达。此外，暴露于 morin 的 SH-SY5Y 细胞能够显著增加 caspase 3 和 9 的基因表达，并增强其裂解，从而引发内在凋亡级联。最后，morin 抑制 NF-κB 的核易位。我们的研究表明 morin 能够降低 SH-SY5Y 细胞的生长，并揭示其作用机制，表明其作为抗癌药物具有广阔的前景。
