a Department of Biochemistry and Molecular Biology, School of Life Sciences , Pondicherry University , Kalapet , Puducherry , India.
b Centre for Bioinformatics, School of Life Sciences , Pondicherry University , Kalapet , Puducherry , India.
Toxicol Mech Methods. 2018 Mar;28(3):205-218. doi: 10.1080/15376516.2017.1388460. Epub 2017 Nov 21.
Metastasis is the major hindrance in the treatment of all cancers, including laryngeal squamous cell carcinoma. Intensive researches are under way to identify the effective natural polyphenols with anti-metastatic ability for cancer treatment. Wheatgrass, an herbal plant has been reported to show anticancer effects. Hence, in this study, we aimed to analyze the anti-metastatic effect of methanol extract of wheatgrass (MEWG). The levels of metastatic marker proteins were determined by western blot. PI3K and AKT levels were determined by real time (RT)-PCR analysis. In silico molecular docking was done to check the interaction of the 14 components (identified by HPLC/GCMS) of MEWG with PI3K and AKT. MEWG effectively decreased the metastatic protein expressions, namely VEGF, MMP-9 and COX-2 and increased TIMP-2. RT-PCR results showed reduced m-RNA levels of both PI3K and AKT when compared to control. Molecular docking studies revealed interaction of most of the identified compounds of the extract with the important residues of PI3K and AKT. These findings indicate that MEWG inhibits metastasis and angiogenesis in Hep-2 cells possibly via PI3K/AKT due to the cumulative effect of polyphenols and other constituent present in extract. The compounds of the extract were also found to be directly involved in inhibition of AKT/PI3K, thus could help to restrain metastasis.
转移是包括喉鳞状细胞癌在内的所有癌症治疗的主要障碍。目前正在进行深入研究，以确定具有抗转移能力的有效天然多酚类化合物，用于癌症治疗。小麦草作为一种草本植物，已被报道具有抗癌作用。因此，在这项研究中，我们旨在分析小麦草甲醇提取物（MEWG）的抗转移作用。通过 Western blot 测定转移标记蛋白的水平。通过实时（RT）-PCR 分析测定 PI3K 和 AKT 水平。通过计算机分子对接检查 MEWG 的 14 种成分（通过 HPLC/GCMS 鉴定）与 PI3K 和 AKT 的相互作用。MEWG 有效降低了转移性蛋白的表达，即 VEGF、MMP-9 和 COX-2，并增加了 TIMP-2。与对照组相比，RT-PCR 结果显示 PI3K 和 AKT 的 m-RNA 水平降低。分子对接研究表明，提取物中大多数鉴定出的化合物与 PI3K 和 AKT 的重要残基相互作用。这些发现表明，由于提取物中多酚类化合物和其他成分的累积效应，MEWG 通过 PI3K/AKT 抑制 Hep-2 细胞的转移和血管生成。提取物中的化合物也被发现直接参与抑制 AKT/PI3K，从而有助于抑制转移。
