Indirubin derivative E804 inhibits angiogenesis
<p>Abstract</p> <p>Background</p> <p>It has previously been shown that indirubin derivative E804 (IDR-E804) blocks signal transducer and activator of transcription-3 signaling in human breast and prostate cancer cells and inhibits Src kinase activity. To further establi...
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| Format: | Article |
| Language: | English |
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BMC
2012-05-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://www.biomedcentral.com/1471-2407/12/164 |
| _version_ | 1818556353073905664 |
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| author | Shin Eun-Kyung Kim Jin-Kyung |
| author_facet | Shin Eun-Kyung Kim Jin-Kyung |
| author_sort | Shin Eun-Kyung |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>It has previously been shown that indirubin derivative E804 (IDR-E804) blocks signal transducer and activator of transcription-3 signaling in human breast and prostate cancer cells and inhibits Src kinase activity. To further establish its role in angiogenesis, we tested its potential using human umbilical vein endothelial cells (HUVECs) and analyzed the effects of IDR-E804 on cellular and molecular events related to angiogenesis.</p> <p>Methods</p> <p>The anti-angiogenic effects of IDR-E804 were examined by assessing the proliferation, migration and capillary tube formation of HUVECs were induced by vascular endothelial growth factor (VEGF) with or without various concentrations of IDR-E804. The inhibitory effect of IDR-E804 angiogenesis and tumor growth <it>in vivo</it> was also investigated in Balb/c mice subcutaneously transplanted with CT-26 colon cancer cells.</p> <p>Results</p> <p>IDR-E804 significantly decreased proliferation, migration and tube formation of vascular endothelial growth factor VEGF-treated HUVECs. These effects were accompanied by decreased phosphorylation of VEGF receptor (VEGFR)-2, AKT and extracellular signal regulated kinase in VEGF-treated HUVECs. Intratumor injections of IDR-E804 inhibited the growth of subcutaneously inoculated CT-26 allografts in syngenic mice. Immunohistochemistry revealed a decreased CD31 microvessel density index and Ki-67 proliferative index, but an increased apoptosis index in IDR-E804-treated tumors.</p> <p>Conclusions</p> <p>These data revealed that IDR-E804 is an inhibitor of angiogenesis and also provide evidence for the efficacy of IDR-E804 for anti-tumor therapies.</p> |
| first_indexed | 2024-12-13T23:46:16Z |
| format | Article |
| id | doaj.art-f66f80a4c00246279495c69fd2f61696 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-13T23:46:16Z |
| publishDate | 2012-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-f66f80a4c00246279495c69fd2f616962022-12-21T23:26:57ZengBMCBMC Cancer1471-24072012-05-0112116410.1186/1471-2407-12-164Indirubin derivative E804 inhibits angiogenesisShin Eun-KyungKim Jin-Kyung<p>Abstract</p> <p>Background</p> <p>It has previously been shown that indirubin derivative E804 (IDR-E804) blocks signal transducer and activator of transcription-3 signaling in human breast and prostate cancer cells and inhibits Src kinase activity. To further establish its role in angiogenesis, we tested its potential using human umbilical vein endothelial cells (HUVECs) and analyzed the effects of IDR-E804 on cellular and molecular events related to angiogenesis.</p> <p>Methods</p> <p>The anti-angiogenic effects of IDR-E804 were examined by assessing the proliferation, migration and capillary tube formation of HUVECs were induced by vascular endothelial growth factor (VEGF) with or without various concentrations of IDR-E804. The inhibitory effect of IDR-E804 angiogenesis and tumor growth <it>in vivo</it> was also investigated in Balb/c mice subcutaneously transplanted with CT-26 colon cancer cells.</p> <p>Results</p> <p>IDR-E804 significantly decreased proliferation, migration and tube formation of vascular endothelial growth factor VEGF-treated HUVECs. These effects were accompanied by decreased phosphorylation of VEGF receptor (VEGFR)-2, AKT and extracellular signal regulated kinase in VEGF-treated HUVECs. Intratumor injections of IDR-E804 inhibited the growth of subcutaneously inoculated CT-26 allografts in syngenic mice. Immunohistochemistry revealed a decreased CD31 microvessel density index and Ki-67 proliferative index, but an increased apoptosis index in IDR-E804-treated tumors.</p> <p>Conclusions</p> <p>These data revealed that IDR-E804 is an inhibitor of angiogenesis and also provide evidence for the efficacy of IDR-E804 for anti-tumor therapies.</p>http://www.biomedcentral.com/1471-2407/12/164AngiogenesisIndirubin derivative E804Vascular endothelial growth factor receptor-2Human umbilical vein endothelial cellsTumor |
| spellingShingle | Shin Eun-Kyung Kim Jin-Kyung Indirubin derivative E804 inhibits angiogenesis BMC Cancer Angiogenesis Indirubin derivative E804 Vascular endothelial growth factor receptor-2 Human umbilical vein endothelial cells Tumor |
| title | Indirubin derivative E804 inhibits angiogenesis |
| title_full | Indirubin derivative E804 inhibits angiogenesis |
| title_fullStr | Indirubin derivative E804 inhibits angiogenesis |
| title_full_unstemmed | Indirubin derivative E804 inhibits angiogenesis |
| title_short | Indirubin derivative E804 inhibits angiogenesis |
| title_sort | indirubin derivative e804 inhibits angiogenesis |
| topic | Angiogenesis Indirubin derivative E804 Vascular endothelial growth factor receptor-2 Human umbilical vein endothelial cells Tumor |
| url | http://www.biomedcentral.com/1471-2407/12/164 |
| work_keys_str_mv | AT shineunkyung indirubinderivativee804inhibitsangiogenesis AT kimjinkyung indirubinderivativee804inhibitsangiogenesis |