{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:54:25Z","timestamp":1785927265629,"version":"3.56.0"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,6]],"date-time":"2020-02-06T00:00:00Z","timestamp":1580947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VALERE: Vanvitelli per la Ricerca Program, the Italian Association for Cancer Research","award":["AIRC-17217"],"award-info":[{"award-number":["AIRC-17217"]}]},{"name":"MIUR20152TE5PK","award":["20152TE5PK"],"award-info":[{"award-number":["20152TE5PK"]}]},{"name":"EPICHEMBIO","award":["CM1406"],"award-info":[{"award-number":["CM1406"]}]},{"name":"Campania Regional Government Lotta alle Patologie Oncologiche iCURE","award":["CUP B21c17000030007"],"award-info":[{"award-number":["CUP B21c17000030007"]}]},{"name":"Campania Regional Government FASE 2: IDEAL","award":["CUP B63D18000560007"],"award-info":[{"award-number":["CUP B63D18000560007"]}]},{"name":"MIUR Proof of Concept","award":["POC01_00043"],"award-info":[{"award-number":["POC01_00043"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Some species of clover are reported to have beneficial effects in human diseases. However, little is known about the activity of the forage plant Trifolium repens, or white clover, which has been recently found to exert a hepatoprotective action. Scientific interest is increasingly focused on identifying new drugs, especially natural products and their derivatives, to treat human diseases including cancer. We analyzed the anticancer effects of T. repens in several cancer cell lines. The phytochemical components of T. repens were first extracted in a methanol solution and then separated into four fractions by ultra-high-performance liquid chromatography. The effects of the total extract and each fraction on cancer cell proliferation were analyzed by MTT assay and Western blotting. T. repens and, more robustly, its isoflavonoid-rich fraction showed high cytotoxic effects in chronic myelogenous leukemia (CML) K562 cells, with IC50 values of 1.67 and 0.092 mg\/mL, respectively. The block of cell growth was associated with a total inhibition of BCR-ABL\/STAT5 and activation of the p38 signaling pathways. In contrast, these strongly cytotoxic effects did not occur in normal cells. Our findings suggest that the development of novel compounds derived from phytochemical molecules contained in Trifolium might lead to the identification of new therapeutic agents active against CML.<\/jats:p>","DOI":"10.3390\/cells9020379","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T03:13:27Z","timestamp":1581045207000},"page":"379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Trifolium Repens Blocks Proliferation in Chronic Myelogenous Leukemia via the BCR-ABL\/STAT5 Pathway"],"prefix":"10.3390","volume":"9","author":[{"given":"Federica","family":"Sarno","sequence":"first","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Pepe","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Pharmacy, University of Salerno, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0272-0901","authenticated-orcid":false,"given":"Pasquale","family":"Termolino","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Bioresources (IBBR), National Research Council of Italy (CNR), 80055 Portici, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8025-3758","authenticated-orcid":false,"given":"Vincenzo","family":"Carafa","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crescenzo","family":"Massaro","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Merciai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Pharmacy, University of Salerno, 84084 Fisciano, Italy"},{"name":"PhD Program in Drug Discovery and Development, University of Salerno, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1069-2181","authenticated-orcid":false,"given":"Pietro","family":"Campiglia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Pharmacy, University of Salerno, 84084 Fisciano, Italy"},{"name":"European Biomedical Research Institute of Salerno, 84125 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5374-3527","authenticated-orcid":false,"given":"Angela","family":"Nebbioso","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7312-5387","authenticated-orcid":false,"given":"Lucia","family":"Altucci","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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