{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:44:57Z","timestamp":1785775497743,"version":"3.56.0"},"reference-count":85,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009687","name":"Wroclaw Medical University","doi-asserted-by":"publisher","award":["SUBK.A412.23.070"],"award-info":[{"award-number":["SUBK.A412.23.070"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"publisher"}]},{"award":["SUBK.A412.23.070"],"award-info":[{"award-number":["SUBK.A412.23.070"]}],"id":[{"id":"https:\/\/ror.org\/01qpw1b93","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Chronic inflammation and cyclooxygenase (COX)-2\u2013mediated prostanoid signaling contribute to melanoma progression, yet their modulation by natural products remains poorly defined. We examined the effects of dogwood fruit extracts\u2014Japanese cornel (Cornus officinalis) and two European cultivars (\u2018Uholok\u2019, \u2018Yantarnyi\u2019)\u2014on temporal prostanoid dynamics in A375 (primary tumor\u2013derived) and MeWo (metastasis-derived) mela-noma cells. Dynamic changes rather than static levels were modeled using GAMLSS or zero-inflated Gamma models to assess time, cell line, cornel type, and dose effects. Untreated A375 cells showed time-dependent increases in PGE2, PGF2\u03b1, thromboxane B2, and 13,14-dihydro-PGE1, consistent with inducible COX-2 activation, whereas MeWo cells maintained consistently high prostanoid levels, reflecting constitutive COX-2 expression. Cornus extracts modulated these trajectories in a cell- and dose-dependent manner. In A375, low concentrations allowed prostanoid accumulation, while higher doses flattened or reversed these increases; Japanese cornel produced the strongest inhibition, whereas European cultivars showed weaker or cultivar-specific effects. MeWo cells were less responsive, with significant changes emerging only at higher doses. PGD2 and 6-keto-PGF1\u03b1 remained largely unchanged, indicating selective targeting of COX-2\u2013dependent prostanoids. Extracts also reduced accumulation of downstream prostanoids, including 15-deoxy-\u039412,14-PGJ2 and 13,14-dihydro-PGE1, particularly in A375 cells. These differences highlight a stronger susceptibility of early-stage melanoma to phytochemical intervention and support cultivar-dependent bioactivity linked to phytochemical composition. In summary, Cornus extracts selectively attenuate time-dependent trajectories of tumor-promoting prostanoids\u2014most effectively with Japanese cornel\u2014while sparing homeostatic mediators, warranting further investigation on their potential for melanoma chemoprevention or adjunctive therapy.<\/jats:p>","DOI":"10.3390\/ijms27156982","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:51:23Z","timestamp":1785772283000},"page":"6982","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Time-Resolved Metabolomics Reveals Distinct, Cell- and Variety-Dependent Profiles of Prostanoids in Melanoma Cells Exposed to Fruit Extracts from Cornus mas and C. officinalis: A Pilot Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7624-631X","authenticated-orcid":false,"given":"\u0141ukasz","family":"Lewandowski","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Immunochemistry, Faculty of Medicine, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Krzystek-Korpacka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunochemistry, Faculty of Medicine, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8563-9625","authenticated-orcid":false,"given":"Daria","family":"Mykhailova","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunochemistry, Faculty of Medicine, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-7067","authenticated-orcid":false,"given":"Martyna","family":"Korbecka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunochemistry, Faculty of Medicine, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Bryk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunochemistry, Faculty of Medicine, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7857-327X","authenticated-orcid":false,"given":"Mariusz","family":"Fleszar","sequence":"additional","affiliation":[{"name":"Omics Research Center, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4617-798X","authenticated-orcid":false,"given":"Paulina","family":"Fortuna","sequence":"additional","affiliation":[{"name":"Omics Research Center, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2172-0408","authenticated-orcid":false,"given":"Alicja Z.","family":"Kucharska","sequence":"additional","affiliation":[{"name":"Department of Fruit, Vegetable and Plant Nutraceutical Technology, Wroclaw University of Environmental and Life Sciences, J. Che\u0142mo\u0144skiego 37, 51-630 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1722-3190","authenticated-orcid":false,"given":"Tomasz","family":"Soza\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Preclinical Sciences, Pharmacology and Medical Diagnostics, Wroclaw University of Science and Technology, Wybrze\u017ce Wyspia\u0144skiego 27, 50-370 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3879-6548","authenticated-orcid":false,"given":"Jolanta","family":"Zalejska-Fiolka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Mosna","sequence":"additional","affiliation":[{"name":"Omics Research Center, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wioleta","family":"Szewczak","sequence":"additional","affiliation":[{"name":"Omics Research Center, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7244-2017","authenticated-orcid":false,"given":"Iwona","family":"Bednarz-Misa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunochemistry, Faculty of Medicine, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ekor, M. 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