School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou 510006, China.
Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Molecules. 2019 Jan 2;24(1):144. doi: 10.3390/molecules24010144.
ViceninII is a naturally flavonoid glycoside extracted from , a precious Chinese traditional herb, has been proven to be valuable for cancer treatment. Transforming growth factor-β1 (TGF-β1), promotes the induction of epithelial⁻mesenchymal transition (EMT), a process involved in the metastasis of cells that leads to enhanced migration and invasion. However, there is no previously evidence that ViceninII has an inhibitory effect on cancer metastasis, specifically on the TGF-β1-induced EMT process in lung adenocarcinoma cells. In this experiment, we used UV, ESIMS, and NMR to identify the structure of ViceninII.A549 and H1299 cells were treated with TGF-β1 in the absence and presence of ViceninII, and subsequent migration and invasion were measured by wound-healing and transwell assays. The protein localization and expressions were detected by immunofluorescence and Western blotting. The results indicated that TGF-β1 induced spindle-shaped changes, increased migration and invasion, and upregulated or downregulated the relative expression of EMT biomarkers. Meanwhile, these alterations were significantly inhibited when co-treated with ViceninII and inhibitors LY294002 and SB431542. In conclusion, ViceninII inhibited TGF-β1-induced EMT via the deactivation of TGF-β/Smad and PI3K/Akt/mTOR signaling pathways.This is the first time that the anti-metastatic effects of ViceninII have been demonstrated, and their molecular mechanisms provided.
二氢杨梅素是从杨梅科植物中提取的一种天然黄酮糖苷,已被证明对癌症治疗有价值。转化生长因子-β1(TGF-β1)促进上皮-间充质转化(EMT)的诱导,这是一个涉及细胞转移的过程,导致迁移和侵袭能力增强。然而,目前尚无证据表明二氢杨梅素有抑制癌症转移的作用,特别是对肺腺癌细胞中 TGF-β1 诱导的 EMT 过程。在本实验中,我们使用 UV、ESIMS 和 NMR 来鉴定二氢杨梅素的结构。用 TGF-β1 处理 A549 和 H1299 细胞,在有无二氢杨梅素的情况下,通过划痕愈合和 Transwell 测定法测量随后的迁移和侵袭。通过免疫荧光和 Western blot 检测蛋白定位和表达。结果表明,TGF-β1 诱导细胞呈纺锤形改变,增加迁移和侵袭,并上调或下调 EMT 标志物的相对表达。同时,当与二氢杨梅素和抑制剂 LY294002 和 SB431542 共同处理时,这些改变明显受到抑制。总之,二氢杨梅素通过抑制 TGF-β/Smad 和 PI3K/Akt/mTOR 信号通路抑制 TGF-β1 诱导的 EMT。这是首次证明二氢杨梅素的抗转移作用,并提供了其分子机制。