{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:01:10Z","timestamp":1789585270435,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T00:00:00Z","timestamp":1547683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803101"],"award-info":[{"award-number":["81803101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010246","name":"Postdoctoral Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["2016M591398"],"award-info":[{"award-number":["2016M591398"]}],"id":[{"id":"10.13039\/501100010246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:p>\n                    Tumor metastasis is still the leading cause of melanoma mortality. Luteolin, a natural flavonoid, is found in fruits, vegetables, and medicinal herbs. The pharmacological action and mechanism of luteolin on the metastasis of melanoma remain elusive. In this study, we investigated the effect of luteolin on A375 and B16\u2010F10 cell viability, migration, invasion, adhesion, and tube formation of human umbilical vein endothelial cells. Epithelial\u2013mesenchymal transition (EMT) markers and pivotal molecules in HIF\u20101\u03b1\/VEGF signaling expression were analysed using western blot assays or quantitative real\u2010time polymerase chain reaction. Results showed that luteolin inhibits cellular proliferation in A375 and B16\u2010F10 melanoma cells in a time\u2010dependent and concentration\u2010dependent manner. Luteolin significantly inhibited the migratory, invasive, adhesive, and tube\u2010forming potential of highly metastatic A375 and B16\u2010F10 melanoma cells or human umbilical vein endothelial cells at sub\u2010IC\n                    <jats:sub>50<\/jats:sub>\n                    concentrations, where no significant cytotoxicity was observed. Luteolin effectively suppressed EMT by increased E\u2010cadherin and decreased N\u2010cadherin and vimentin expression both in mRNA and protein levels. Further, luteolin exerted its anti\u2010metastasis activity through decreasing the p\u2010Akt, HIF\u20101\u03b1, VEGF\u2010A, p\u2010VEGFR\u20102, MMP\u20102, and MMP\u20109 proteins expression. Overall, our findings first time suggests that HIF\u20101\u03b1\/VEGF signaling\u2010mediated EMT and angiogenesis is critically involved in anti\u2010metastasis effect of luteolin as a potential therapeutic candidate for melanoma.\n                  <\/jats:p>","DOI":"10.1002\/ptr.6273","type":"journal-article","created":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T13:02:24Z","timestamp":1547730144000},"page":"798-807","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["HIF\u20101\u03b1\/VEGF signaling\u2010mediated epithelial\u2013mesenchymal transition and angiogenesis is critically involved in anti\u2010metastasis effect of luteolin in melanoma cells"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8266-588X","authenticated-orcid":false,"given":"Chunyu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Integrated Chinese Traditional and Western Medicine, International Medical School Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology Shanghai Pulmonary Hospital Affiliated Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Integrated Chinese Traditional and Western Medicine, International Medical School Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolu","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Integrated Chinese Traditional and Western Medicine, International Medical School Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Integrated Chinese Traditional and Western Medicine, International Medical School Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3923\/pjbs.2011.821.830"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2018.05.019"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-016-9826-6"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/1547691X.2012.723767"},{"key":"e_1_2_7_6_1","first-page":"89","article-title":"Mechanism of metastasis suppression by luteolin in breast cancer","volume":"10","author":"Cook M. 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