AIMS: This study was designed to evaluate the antiangiogenic properties of emodin and its ability to inhibit tyrosine-kinase-mediated phosphorylation of vascular endothelial growth factor (VEGF) receptors in colon cancer cells. METHODS: The effects of emodin on VEGF-receptor (VEGFR) phosphorylation were determined by assaying the tyrosine kinase activity and by Western blot analysis. The antiproliferative and proapoptotic activities of emodin were evaluated by soft agar colony formation, flow cytometric analysis of cell cycle, and by apoptotic assay. RESULTS: Emodin causes a dose-dependent inhibition of VEGFR phosphorylation in colon cancer cells. Treatment with 40 muM of emodin decreased the relative activity of VEGFR-1 to 22.4%, when compared to the control group (assigned a value of 100%); VEGFR-2 and -3 showed a similar reduction in relative activity at 58.5% and 31.6%, respectively (p < 0.01, in each case). Treatment with emodin reduced VEGFR phosphorylation, as evidenced by Western blot analysis. Flow cytometric analysis showed that, upon treatment with emodin, the HCT116 cell cycle was blocked at the G2/M phase. Emodin also increased the apoptosis of HCT116 cells in a dose-dependent manner; treatment with 40 muM emodin increased the apoptotic rate from 8.1% +/- 2.7% in the control group to 27.8% +/- 10.9% in the treated group (p < 0.01). CONCLUSIONS: These studies demonstrate that emodin may inhibit cancer-cell growth by blocking VEGFR signaling and indicate that emodin can be used as a potential inhibitor for tumor angiogenesis.
AIMS: This study was designed to evaluate the antiangiogenic properties of emodin and its ability to inhibit tyrosine-kinase-mediated phosphorylation of vascular endothelial growth factor (VEGF) receptors in colon cancer cells. METHODS: The effects of emodin on VEGF-receptor (VEGFR) phosphorylation were determined by assaying the tyrosine kinase activity and by Western blot analysis. The antiproliferative and proapoptotic activities of emodin were evaluated by soft agar colony formation, flow cytometric analysis of cell cycle, and by apoptotic assay. RESULTS: Emodin causes a dose-dependent inhibition of VEGFR phosphorylation in colon cancer cells. Treatment with 40 muM of emodin decreased the relative activity of VEGFR-1 to 22.4%, when compared to the control group (assigned a value of 100%); VEGFR-2 and -3 showed a similar reduction in relative activity at 58.5% and 31.6%, respectively (p < 0.01, in each case). Treatment with emodin reduced VEGFR phosphorylation, as evidenced by Western blot analysis. Flow cytometric analysis showed that, upon treatment with emodin, the HCT116 cell cycle was blocked at the G2/M phase. Emodin also increased the apoptosis of HCT116 cells in a dose-dependent manner; treatment with 40 muM emodin increased the apoptotic rate from 8.1% +/- 2.7% in the control group to 27.8% +/- 10.9% in the treated group (p < 0.01). CONCLUSIONS: These studies demonstrate that emodin may inhibit cancer-cell growth by blocking VEGFR signaling and indicate that emodin can be used as a potential inhibitor for tumor angiogenesis.