{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T07:11:42Z","timestamp":1780989102444,"version":"3.54.1"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,8,30]],"date-time":"2014-08-30T00:00:00Z","timestamp":1409356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Veterans Administration Merit Review Award","award":["1I01BX001410"],"award-info":[{"award-number":["1I01BX001410"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>Cutaneous malignant melanoma is the leading cause of death from skin diseases and is often associated with activating mutations of the proto\u2010oncogene <jats:italic>BRAF<\/jats:italic>. To develop more effective strategies for the prevention or treatment of melanoma, we have examined the inhibitory effects of silymarin, a flavanoid from <jats:italic>Silybum marianum<\/jats:italic>, on melanoma cells. Using A375 (<jats:italic>BRAF<\/jats:italic>\u2010mutated) and Hs294t (non <jats:italic>BRAF<\/jats:italic>\u2010mutated but highly metastatic) human melanoma cell lines, we found that in vitro treatment with silymarin resulted in a dose\u2010dependent: (<jats:italic>i<\/jats:italic>) reduction in cell viability; (<jats:italic>ii<\/jats:italic>) enhancement of either Go\/G1 (A375) or G2\u2010M (Hs294t) phase cell cycle arrest with corresponding alterations in cyclins and cyclin\u2010dependent kinases; and (<jats:italic>iii<\/jats:italic>) induction of apoptosis. The silymarin\u2010induced apoptosis of human melanoma cells was associated with a reduction in the levels of anti\u2010apoptotic proteins (Bcl\u20102 and Bcl\u2010xl), an increase in the levels of pro\u2010apoptotic protein (Bax), and activation of caspases. Further, oral administration of silymarin (500\u2009mg\/kg body weight\/2\u00d7 a week) significantly inhibited (60%, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01) the growth of <jats:italic>BRAF<\/jats:italic>\u2010mutated A375 melanoma tumor xenografts, and this was associated with: (<jats:italic>i<\/jats:italic>) inhibition of cell proliferation; (<jats:italic>ii<\/jats:italic>) induction of apoptosis of tumor cells; (<jats:italic>iii<\/jats:italic>) alterations in cell cycle regulatory proteins; and (<jats:italic>iv<\/jats:italic>) reduced expression of tumor angiogenic biomarkers in tumor xenograft tissues. These results indicate that silymarin may have a chemotherapeutic effect on human melanoma cell growth and warrant its further evaluation. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22208","type":"journal-article","created":{"date-parts":[[2014,8,31]],"date-time":"2014-08-31T01:27:40Z","timestamp":1409448460000},"page":"1328-1339","source":"Crossref","is-referenced-by-count":36,"title":["Silymarin inhibits melanoma cell growth both in vitro and in vivo by targeting cell cycle regulators, angiogenic biomarkers and induction of apoptosis"],"prefix":"10.1002","volume":"54","author":[{"given":"Mudit","family":"Vaid","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Alabama at Birmingham Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tripti","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Alabama at Birmingham Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Alabama at Birmingham Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh K.","family":"Katiyar","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Alabama at Birmingham Birmingham Alabama"},{"name":"Birmingham Veterans Affairs Medical Center Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,30]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"American Cancer Society. 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