Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan, Republic of China.
Expert Opin Ther Targets. 2013 Apr;17(4):337-49. doi: 10.1517/14728222.2013.756869. Epub 2013 Jan 18.
Isoliquiritigenin (ISL) is a natural phenolic compound extracted from licorice. Previous studies have shown that ISL is a potent antioxidant with anti-inflammatory and antitumor activities. The anti-invasive activity of ISL was still unclear. The actual causes of death for most breast cancer patients were due to the tumor metastasis. Attenuating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) is well known to prevent tumor metastasis.
The purpose of this study is to investigate the effects of ISL on VEGF and MMP expression in highly metastatic human breast cancer cell line, MDA-MB-231.
ISL reduced the secretions and protein levels of VEGF. The VEGF upstream regulatory protein, hypoxia-inducible factor 1-alpha (HIF-1α), was also reduced after ISL treatment. Moreover, ISL inhibited the expression and gelatinolytic activity of MMP-2 and MMP-9 which were confirmed by western blot and gelatin zymography assay. Additionally, the anti-migratory activity of ISL was further confirmed by chamber migration assay and wound migration assay. Upstream signaling pathways, including the expression of phosphatidylinositol-3 kinase (PI3K), the phosphorylation of p38 and Akt kinase and NF-κB DNA binding activity, were suppressed by ISL.
These findings suggest that ISL suppresses the migration of MDA-MB-231 cells by inhibiting the upstream signaling pathways.
异甘草素（ISL）是从甘草中提取的天然酚类化合物。先前的研究表明，ISL 是一种有效的抗氧化剂，具有抗炎和抗肿瘤活性。ISL 的抗侵袭活性尚不清楚。大多数乳腺癌患者的死亡实际原因是肿瘤转移。降低血管内皮生长因子（VEGF）和基质金属蛋白酶（MMPs）的表达已被证明可预防肿瘤转移。
本研究旨在探讨 ISL 对高转移性人乳腺癌细胞系 MDA-MB-231 中 VEGF 和 MMP 表达的影响。
ISL 降低了 VEGF 的分泌和蛋白水平。ISL 处理后，VEGF 的上游调节蛋白缺氧诱导因子 1-α（HIF-1α）也减少。此外，通过 Western blot 和明胶酶谱分析证实，ISL 抑制了 MMP-2 和 MMP-9 的表达和明胶酶活性。此外，通过室迁移试验和划痕迁移试验进一步证实了 ISL 的抗迁移活性。ISL 还抑制了磷脂酰肌醇-3 激酶（PI3K）的表达、p38 和 Akt 激酶的磷酸化以及 NF-κB DNA 结合活性等上游信号通路。
这些发现表明，ISL 通过抑制上游信号通路抑制 MDA-MB-231 细胞的迁移。
