{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:32:00Z","timestamp":1790249520871,"version":"4.1.0"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Melanoma is the most aggressive form of skin cancer and the most rapidly expanding cancer in terms of worldwide incidence. If primary cutaneous melanoma is mostly treated with a curative wide local excision, malignant melanoma has a poor prognosis and needs other therapeutic approaches. Angiogenesis is a normal physiological process essential in growth and development, but it also plays a crucial role in crossing from benign to advanced state in cancer. In melanoma progression, angiogenesis is widely involved during the vertical growth phase. Currently, no anti-angiogenic agents are efficient on their own, and combination of treatments will probably be the key to success. In the past, phenacetin\u00a0was used as an analgesic to relieve pain, causing side effects at large dose and tumor-inducing in humans and animals. By contrast, <jats:italic>Phenacetinum<\/jats:italic> low-dilution is often used in skin febrile exanthema, patches profusely scattered on limbs, headache, or flushed face without side effects. Herein are described the <jats:italic>in vitro<\/jats:italic>, <jats:italic>in vivo<\/jats:italic>, and <jats:italic>ex vivo<\/jats:italic> anti-angiogenic and anti-tumoral potentials of <jats:italic>Phenacetinum<\/jats:italic> low-dilution in a B16F1 tumor model and endothelial cells. We demonstrate that low-diluted <jats:italic>Phenacetinum<\/jats:italic> inhibits <jats:italic>in vivo<\/jats:italic> tumor growth and tumor vascularization and thus increases the survival time of B16F1 melanoma induced-C57BL\/6 mice. Moreover, <jats:italic>Phenacetinum<\/jats:italic> modulates the lung metastasis in a B16F10 induced model. <jats:italic>Ex vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>, we evidence that low-diluted <jats:italic>Phenacetinum<\/jats:italic> inhibits the migration and the recruitment of endothelial cells and leads to an imbalance in the pro-tumoral macrophages and to a structural malformation of the vascular network. All together these results demonstrate highly hopeful anti-tumoral, anti-metastatic, and anti-angiogenic effects of <jats:italic>Phenacetinum<\/jats:italic> low-dilution on melanoma. Continued studies are needed to preclinically validate <jats:italic>Phenacetinum<\/jats:italic> low-dilution as a complementary or therapeutic strategy for melanoma treatment.<\/jats:p>","DOI":"10.3389\/fonc.2021.597503","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T05:36:45Z","timestamp":1614749805000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Anti-Tumoral and Anti-Angiogenic Effects of Low-Diluted Phenacetinum on Melanoma"],"prefix":"10.3389","volume":"11","author":[{"given":"Camille","family":"Fuselier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Quemener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonore","family":"Dufay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Bour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Boulagnon-Rombi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Bouland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El-Hadi","family":"Djermoune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Devy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Martiny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1056\/NEJMra052166","article-title":"Melanoma","volume":"355","author":"Miller","year":"2006","journal-title":"N 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