title: The anthraquinone derivative Emodin inhibits angiogenesis and metastasis through downregulating Runx2 activity in breast cancer.
abstract: Emodin (EMD) is an anthraquinone derivative extracted from the root and rhizome of Rheum palmatum L. which exhibits a range of activities, including anti-bacterial, antitumor, diuretic and vasorelaxant effects. The ability to inhibit metastasis and angiogenesis was shown in previous pharmacological studies, but clear information to address EMD affecting angiogenesis and metastasis in human breast cancer is still lacking. In the present study, we evaluated a possible role for EMD in angiogenesis and metastasis induced by breast cancer cells. It was revealed here that EMD attenuated tumor cell-induced metastasis and angiogenesis both in vitro and in vivo. Furthermore, it was found that these inhibitory effects were caused by MMPs and VEGFR-2 inhibition in metastatic breast cancer cells and endothelial cells, respectively. Western blot analysis showed reduction of Runx2 activation in the EMD-treated cells. ELISA based Runx2 transcription factor assay showed that the interaction between Runx2 and target sequences was inhibited by EMD. Our findings suggested that the inhibitory effects of EMD on tumor-induced metastasis and angiogenesis were caused by MMPs and VEGFR-2 inhibition, which may be associated with the downregulation of Runx2 transcriptional activity.
authors: Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China.
authors: Junchao
authors: J
authors: Ma
authors: Modern Education Technology Center, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China.
authors: Hong
authors: H
authors: Lu
authors: Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China.
authors: Shan
authors: S
authors: Wang
authors: Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China.
authors: Bin
authors: B
authors: Chen
authors: Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China.
authors: Zhaojie
authors: Z
authors: Liu
authors: Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China.
authors: Xiaoqin
authors: X
authors: Ke
authors: Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China.
authors: Ting
authors: T
authors: Liu
authors: Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China.
authors: Jianjiang
authors: J
authors: Fu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D015536:Down-Regulation; D004642:Emodin / Q000008:administration & dosage* / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary*; D051379:Mice; D016513:Mice, SCID; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; D004642:Emodin