Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Food Funct. 2018 Dec 13;9(12):6196-6204. doi: 10.1039/c8fo01643g.
Licochalcone A (LicA) has been reported to possess antitumor properties. However, its effect on human glioma cells remains unknown. In this study, we observed that LicA significantly suppressed the ADAM9 expression and the migration and invasion activities of human glioma cells (M059K, U-251 MG, and GBM8901) and exhibited no cell cytotoxicity. The human proteinase antibody array and immunoblot analysis indicated that the LicA treatment inhibited the expression of ADAM9 protein in human glioma cells. Recombinant human ADAM-9 (Rh-ADAM9) treatment significantly reversed the LicA-induced reduction in the ADAM9 level and the migration and invasion activities of human glioma cells. Additionally, the phosphorylation/activation of the mitogen-activated protein kinase kinase (MEK)-extracellularly responsive kinases (ERK) signaling pathway was significantly suppressed in LicA-treated human glioma cells. Cotreatment with LicA and PD98059 synergistically inhibited the ADAM9 expression, cell migration, and cell invasion, which suggested that the MEK-ERK signaling pathway was involved in the LicA-induced inhibition of the ADAM9 expression and the invasion activity of human glioma cells. These findings are the first evidence of LicA's anti-invasive properties against human glioma cells.
甘草查尔酮 A（LicA）已被报道具有抗肿瘤特性。然而，其对人神经胶质瘤细胞的作用尚不清楚。在本研究中，我们观察到 LicA 显著抑制了人神经胶质瘤细胞（M059K、U-251 MG 和 GBM8901）中 ADAM9 的表达以及迁移和侵袭活性，且无细胞毒性。人蛋白水解酶抗体阵列和免疫印迹分析表明 LicA 处理抑制了人神经胶质瘤细胞中 ADAM9 蛋白的表达。重组人 ADAM-9（Rh-ADAM9）处理显著逆转了 LicA 诱导的 ADAM9 水平降低以及人神经胶质瘤细胞的迁移和侵袭活性。此外，LicA 处理的人神经胶质瘤细胞中丝裂原激活的蛋白激酶激酶（MEK）-细胞外反应激酶（ERK）信号通路的磷酸化/激活被显著抑制。LicA 与 PD98059 共同处理协同抑制 ADAM9 的表达、细胞迁移和细胞侵袭，这表明 MEK-ERK 信号通路参与了 LicA 诱导的 ADAM9 表达抑制和人神经胶质瘤细胞的侵袭活性。这些发现是 LicA 抗人神经胶质瘤细胞侵袭特性的首个证据。
