{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:57:23Z","timestamp":1790618243444,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Bufalin (BF) exhibits anti\u2010tumor activity in many tumor types. However, there are few reports on BF in melanoma, and its pharmacological effects have not yet been elucidated. The present study aimed to investigate the effects of BF on melanoma and angiogenesis and to explore its possible mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cell viability in melanoma was assessed by Cell Counting Kit\u20108 (CCK\u20108) and colony formation assays. Flow cytometry was used to evaluate cell cycle and apoptosis. The migration and invasion were detected via the scratch test and transwell chamber migration assay. Bioinformatics analysis and molecular docking were performed to predict the potential BF target. Western blotting was conducted to discover the related protein expressions. To evaluate the antitumor activity of bufalin in\u00a0vivo, subcutaneous xenograft models were established using A375 tumor cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>BF had an inhibitory effect on the growth of melanoma cells and arrested cell cycles in the G2\/M phase. Annexin V\u2010FITC\/PI staining assay indicated that BF can promote apoptosis. BF also repressed human umbilical vein endothelial cell growth, migration, and tubular structure formation. Bioinformatics analysis suggested that BF inhibition in melanoma may be regulated by the PI3K\u2010AKT signaling pathway. Molecular docking results showed that BF forms a hydrogen bond with AKT1. Western blot analysis revealed that BF repressed the phosphorylated AKT protein level. Bufalin inhibits melanoma tumor growth in a xenograft mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study results demonstrated that BF exerts antitumor activity both in\u00a0vitro and in\u00a0vivo. Molecular docking and western blot analysis showed that BF plays an anti\u2010tumor role by downregulating the expression of p\u2010AKT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cnr2.70674","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:07:13Z","timestamp":1788869233000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bufalin Inhibits Melanoma Progression and Endothelial Angiogenic Phenotypes via\n                    <scp>AKT<\/scp>\n                    Signaling"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1106-2586","authenticated-orcid":false,"given":"Xiao xuan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Dermatology Dalian Dermatosis Hospital  Dalian Liaoning P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5252-0622","authenticated-orcid":false,"given":"Ming xin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology Dalian Dermatosis Hospital  Dalian Liaoning P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5937-2154","authenticated-orcid":false,"given":"Jiang xue","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Dalian Dermatosis Hospital  Dalian Liaoning P. R. 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