The anthraquinone derivative Emodin inhibits angiogenesis and metastasis through downregulating Runx2 activity in breast cancer

Ma,Junchao; Lu,Hong; Wang,Shan; Chen,Bin; Liu,Zhaojie; Ke,Xiaoqin; Liu,Ting; Fu,Jianjiang

doi:10.3892/ijo.2015.2888

The anthraquinone derivative Emodin inhibits angiogenesis and metastasis through downregulating Runx2 activity in breast cancer

Authors:
- Junchao Ma
- Hong Lu
- Shan Wang
- Bin Chen
- Zhaojie Liu
- Xiaoqin Ke
- Ting Liu
- Jianjiang Fu
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Affiliations: Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China, Modern Education Technology Center, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China
Published online on: February 10, 2015 https://doi.org/10.3892/ijo.2015.2888
Pages: 1619-1628

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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.

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