Antitumor Effects of Trimethylellagic Acid Isolated From Sanguisorba officinalis L. on Colorectal Cancer via Angiogenesis Inhibition and Apoptosis Induction

作者：Chongfei Bai, Yueshan Sun, Xianchao Pan, Jing Yang, Xiaoxuan Li, Anguo Wu, Dalian Qin, Shousong Cao, Wenjun Zou, Jianming Wu · 发表于：Frontiers in Pharmacology · 年份：2020 · DOI：10.3389/fphar.2019.01646 · 被引用次数：28 · 研究领域：Angiogenesis and VEGF in Cancer、Cancer, Hypoxia, and Metabolism、Cancer Treatment and Pharmacology

Previous studies have demonstrated that tannin could inhibit the proliferation and angiogenesis of cancer cells. However, the mechanism(s) associated with its antitumor effect remains unclear. Here, we investigated the effects of 3,3’,4’-trimethylellagic acid (TMEA), a tannin compound isolated from Sanguisorba officinalis L., on the proliferation, angiogenesis, and apoptosis in cancer cells, as well as the underlying mechanism(s) related to its antitumor activity. TMEA was isolated from Sanguisorba officinalis L. by silica gel column chromatography. Molecular docking was carried out to assess active pocket binding between TMEA and vascular endothelial growth factor receptor 2 (VEGFR2). The antiangiogenic effect of TMEA on the migration and tube formation was detected in HUVECs by wound healing and tube formation assays, respectively. The antitumor effects of TMEA on the cell proliferation were determined in HepG2, A549, and SW620 cells by MTS assay in vitro and on the tumor growth of SW620 xenografts bearing in nude mice in vivo. The mRNA expression of Bcl-2, Bax, caspase-3, VEGF, PI3K, and mTOR were measured by qRT-PCR and protein expression of CD31, Bcl-2, Bax, caspase-3, VEGF, PI3K, and mTOR by immunohistochemical analysis, respectively. The results showed that TMEA combined with VEGFR2 in the functional pockets of Asn223A, Gly922A, and Leu840A and inhibited the migration, tube formation, and expression of VEGF and its downstream signaling mediators in HUVECs. TMEA also si...