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.

Anthraquinones and Derivatives from Marine-Derived Fungi: Structural Diversity and Selected Biological Activities

“…The tumor inhibition rates were higher in the latter two groups than that in low-dose emodin group. It was also revealed that emodin attenuated tumor cell-induced metastasis and angiogenesis, both in vitro and in vivo [ 205 ]. Finally, emodin has been reported to inhibit the growth of pancreatic cancer PANC-1 cells, which may be related to the demethylation of tumor suppressor genes.…”

Effect of semaphorin 3A expression on clinicopathological features and prognosis in oropharyngeal carcinoma

“…CD34 antibody is a credible marker for MVD evaluation. Recent studies have found associations between MVD and poor disease course in breast, lung, stomach, and bladder cancer [35] [36] [37].…”

A marine sponge associated fungal metabolite monacolin X suppresses angiogenesis by down regulating VEGFR2 signaling

“…Our results were similar to Ma J et al and Guan YY et al showed the anthraquinone derivative emodin and Raddeanin A downregulating VEGFR2 activity in breast cancer and colorectal tumor rat model in vivo. 71,72 Molecular docking based virtual screenings using a protein target with experimentally determined structures are in lead discovery for various drug developments. 73 Molecular dynamic simulation is a standard tool for understanding physical interaction between a receptor and ligand (small molecule) in drug discovery.…”