https://scholars.lib.ntu.edu.tw/handle/123456789/535601
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Tai, Huai-Ching | en_US |
dc.contributor.author | TZONG-HUEI LEE | en_US |
dc.contributor.author | Tang, Chih-Hsin | en_US |
dc.contributor.author | Chen, Lei-Po | en_US |
dc.contributor.author | Chen, Wei-Cheng | en_US |
dc.contributor.author | Lee, Ming-Shian | en_US |
dc.contributor.author | Chen, Pei-Chi | en_US |
dc.contributor.author | Lin, Chih-Yang | en_US |
dc.contributor.author | Chi, Chih-Wen | en_US |
dc.contributor.author | Chen, Yu-Jen | en_US |
dc.contributor.author | Lai, Cheng-Ta | en_US |
dc.contributor.author | Chen, Shiou-Sheng | en_US |
dc.contributor.author | Liao, Kuang-Wen | en_US |
dc.contributor.author | Lee, Chien-Hsing | en_US |
dc.contributor.author | Wang, Shih-Wei | en_US |
dc.creator | Tai, H.-C.;Lee, T.-H.;Tang, C.-H.;Chen, L.-P.;Chen, W.-C.;Lee, M.-S.;Chen, P.-C.;Lin, C.-Y.;Chi, C.-W.;Chen, Y.-J.;Lai, C.-T.;Chen, S.-S.;Liao, K.-W.;Lee, C.-H.;Wang, S.-W. | - |
dc.date.accessioned | 2020-12-29T08:15:27Z | - |
dc.date.available | 2020-12-29T08:15:27Z | - |
dc.date.issued | 2019 | - |
dc.identifier.issn | 16603397 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.url?eid=2-s2.0-85064406124&partnerID=40&md5=01f967c5de3e1bf0ee75f6e5100ff667 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/535601 | - |
dc.description.abstract | Lymphangiogenesis is an important biological process associated with cancer metastasis. The development of new drugs that block lymphangiogenesis represents a promising therapeutic strategy. Marine fungus-derived compound phomaketide A, isolated from the fermented broth of Phoma sp. NTOU4195, has been reported to exhibit anti-angiogenic and anti-inflammatory effects. However, its anti-lymphangiogenic activity has not been clarified to date. In this study, we showed that phomaketide A inhibited cell growth, migration, and tube formation of lymphatic endothelial cells (LECs) without an evidence of cytotoxicity. Mechanistic investigations revealed that phomaketide A reduced LECs-induced lymphangiogenesis via vascular endothelial growth factor receptor-3 (VEGFR-3), protein kinase C (PKC), and endothelial nitric oxide synthase (eNOS) signalings. Furthermore, human proteome array analysis indicated that phomaketide A significantly enhanced the protein levels of various protease inhibitors, including cystatin A, serpin B6, tissue factor pathway inhibitor (TFPI), and tissue inhibitor matrix metalloproteinase 1 (TIMP-1). Importantly, phomaketide A impeded tumor growth and lymphangiogenesis by decreasing the expression of LYVE-1, a specific marker for lymphatic vessels, in tumor xenograft animal model. These results suggest that phomaketide A may impair lymphangiogenesis by suppressing VEGFR-3, PKC, and eNOS signaling cascades, while simultaneously activating protease inhibitors in human LECs. We document for the first time that phomaketide A inhibits lymphangiogenesis both in vitro and in vivo, which suggests that this natural product could potentially treat cancer metastasis. ? 2019 by the authors. | - |
dc.relation.ispartof | Marine Drugs | - |
dc.subject | Lymphangiogenesis; Lymphatic endothelial cells; Phomaketide a; Vascular endothelial growth factor receptor-3 | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | antineoplastic agent; endothelial nitric oxide synthase; fungal extract; phomaketide A; protein kinase C delta; rapamycin; unclassified drug; vasculotropin receptor 3; angiogenesis inhibitor; antinematodal agent; endothelial nitric oxide synthase; FLT4 protein, human; NOS3 protein, human; polyketide; PRKCD protein, human; protein kinase C delta; vasculotropin receptor 3; animal experiment; animal model; animal tissue; antineoplastic activity; Article; cancer inhibition; controlled study; drug identification; drug isolation; drug mechanism; drug structure; endothelium cell; human; human cell; lung adenocarcinoma; lymph vessel endothelium; lymphangiogenesis; male; metastasis inhibition; migration inhibition; mouse; nonhuman; Phoma; tumor vascularization; A-549 cell line; animal; aquatic species; Ascomycetes; chemistry; cytology; drug effect; drug screening; endothelium cell; isolation and purification; lymph node metastasis; lymph vessel; lymphangiogenesis; metabolism; neoplasm; nude mouse; pathology; signal transduction; A549 Cells; Angiogenesis Inhibitors; Animals; Antinematodal Agents; Aquatic Organisms; Ascomycota; Endothelial Cells; Humans; Lymphangiogenesis; Lymphatic Metastasis; Lymphatic Vessels; Male; Mice; Mice, Nude; Neoplasms; Nitric Oxide Synthase Type III; Polyketides; Protein Kinase C-delta; Signal Transduction; Vascular Endothelial Growth Factor Receptor-3; Xenograft Model Antitumor Assays | - |
dc.title | Phomaketide A inhibits lymphangiogenesis in human lymphatic endothelial cells | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.3390/md17040215 | - |
dc.identifier.pmid | 30959907 | - |
dc.identifier.scopus | 2-s2.0-85064406124 | - |
dc.relation.journalvolume | 17 | - |
dc.relation.journalissue | 4 | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
crisitem.author.dept | Fisheries Science | - |
crisitem.author.dept | Life Science | - |
crisitem.author.orcid | 0000-0001-8036-7563 | - |
crisitem.author.parentorg | College of Life Science | - |
crisitem.author.parentorg | College of Life Science | - |
顯示於: | 漁業科學研究所 |
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