{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:38:18Z","timestamp":1787611098775,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,3,2]],"date-time":"2018-03-02T00:00:00Z","timestamp":1519948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education","award":["NRF-2016R1D1A1B03932956"],"award-info":[{"award-number":["NRF-2016R1D1A1B03932956"]}]},{"name":"International Joint Research Project of the NST (National Research Council of Science &amp; Technology)","award":["ASIA-16-011"],"award-info":[{"award-number":["ASIA-16-011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Angiogenesis plays a very important role in tumor progression through the creation of new blood vessels. Therefore, angiogenesis inhibitors could contribute to cancer treatment. Here, we show that a microbial metabolite, elaiophylin, exhibits potent antiangiogenic activity from in vitro and in vivo angiogenesis assays. Elaiophylin dramatically suppressed in vitro angiogenic characteristics such as proliferation, migration, adhesion, invasion and tube formation of human umbilical vein endothelial cells (HUVECs) stimulated by vascular endothelial growth factor (VEGF) at non-toxic concentrations. In addition, elaiophylin immensely inhibited in vivo angiogenesis of the chorioallantoic membrane (CAM) from growing chick embryos without cytotoxicity. The activation of VEGF receptor 2 (VEGFR2) in HUVECs by VEGF was inhibited by elaiophylin, resulting in the suppression of VEGF-induced activation of downstream signaling molecules, Akt, extracellular signal-regulated kinase 1\/2 (ERK1\/2), c-Jun N-terminal kinase (JNK), p38, nuclear factor-\u03baB (NF\u03baB), matrix metalloproteinase (MMP)-2 and -9 which are closely associated with VEGF-induced angiogenesis. We also found that elaiophylin blocked tumor cell-induced angiogenesis both in vitro and in vivo. Elaiophylin downregulated the expression of VEGF by inhibiting hypoxia inducible factor-1\u03b1 (HIF-1\u03b1) accumulation in tumor cells. To our knowledge, these results for the first time demonstrate that elaiophylin effectively inhibits angiogenesis and thus may be utilized as a new class of natural antiangiogenic agent for cancer therapy.<\/jats:p>","DOI":"10.3390\/molecules23030563","type":"journal-article","created":{"date-parts":[[2018,3,2]],"date-time":"2018-03-02T11:53:40Z","timestamp":1519991620000},"page":"563","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Antiangiogenic Potential of Microbial Metabolite Elaiophylin for Targeting Tumor Angiogenesis"],"prefix":"10.3390","volume":"23","author":[{"given":"Haet","family":"Lim","sequence":"first","affiliation":[{"name":"Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, Tangjeong-myeon, Asan-si, Chungnam 336-708, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Pil","family":"Jang","sequence":"additional","affiliation":[{"name":"Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jang","family":"Han","sequence":"additional","affiliation":[{"name":"Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, Tangjeong-myeon, Asan-si, Chungnam 336-708, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hyuk","family":"Jang","sequence":"additional","affiliation":[{"name":"Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong","family":"Ahn","sequence":"additional","affiliation":[{"name":"Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, Tangjeong-myeon, Asan-si, Chungnam 336-708, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1056\/NEJM199512283332608","article-title":"Seminars in Medicine of the Beth Israel Hospital, Boston. 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