{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:28:43Z","timestamp":1777498123687,"version":"3.51.4"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,7,24]],"date-time":"2018-07-24T00:00:00Z","timestamp":1532390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bornyl cis-4-hydroxycinnamate, a bioactive compound isolated from Piper betle stems, has the potential for use as an anti-cancer agent. This study investigated the effects of bornyl cis-4-hydroxycinnamate on cell migration and invasion in melanoma cells. Cell migration and invasion were compared in A2058 and A375 melanoma cell lines treated with\/without bornyl cis-4-hydroxycinnamate (1\u20136 \u00b5M). To examine whether bornyl cis-4-hydroxycinnamate has a potential anti-metastatic effect on melanoma cells, cell migration and invasion assays were performed using a Boyden chamber assay and a transwell chamber in A2058 and A375 cells. Gelatin zymography was employed to determine the enzyme activities of MMP-2 and MMP-9. Cell lysates were collected for Western blotting analysis of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors of metalloproteinase-1\/2 (TIMP-1\/2), as well as key molecules in the mitogen-activated protein kinase (MAPK), focal adhesion kinase (FAK)\/ phosphatidylinositide-3 kinases (PI3K)\/Akt\/ mammalian target of rapamycin (mTOR), growth factor receptor-bound protein 2 (GRB2) signaling pathways. Our results demonstrated that bornyl cis-4-hydroxycinnamate is a potentially useful agent that inhibits melanoma cell migration and invasion, and altered melanoma cell metastasis by reducing MMP-2 and MMP-9 expression through inhibition of the FAK\/PI3K\/Akt\/mTOR, MAPK, and GRB2 signaling pathways. Moreover, bornyl cis-4-hydroxycinnamate inhibited the process of the epithelial-to-mesenchymal transition in A2058 and A375 melanoma cells. These findings suggested that bornyl cis-4-hydroxycinnamate has potential as a chemotherapeutic agent, and warrants further investigation for its use in the management of human melanoma.<\/jats:p>","DOI":"10.3390\/ijms19082152","type":"journal-article","created":{"date-parts":[[2018,7,24]],"date-time":"2018-07-24T11:51:38Z","timestamp":1532433098000},"page":"2152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Bornyl cis-4-Hydroxycinnamate Suppresses Cell Metastasis of Melanoma through FAK\/PI3K\/Akt\/mTOR and MAPK Signaling Pathways and Inhibition of the Epithelial-to-Mesenchymal Transition"],"prefix":"10.3390","volume":"19","author":[{"given":"Tzu-Yen","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Food Science, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Li","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Food Science, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi-I","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-I","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nursing, Mei-ho University, Pingtung 91202, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Te-Chih","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Nursing, Mei-ho University, Pingtung 91202, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Jen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biological Technology, Meiho University, Pingtung 91202, Taiwan"},{"name":"Department of Beauty Science, Meiho University, Pingtung 91202, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3322\/canjclin.55.2.74","article-title":"Global cancer statistics, 2002","volume":"55","author":"Parkin","year":"2005","journal-title":"CA Cancer J. 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