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In this study, we demonstrate that the novel Ras antagonist farnesylthiosalicylic acid (FTS) inhibits the growth of Colo 853 melanoma cells through a combination of cytostatic and pro\u2010apoptotic effects. Furthermore, these phenomena are seen under conditions of cell attachment and in the presence of serum. Treatment of Colo 853 cells with FTS led to time\u2010dependent inhibition of constitutive Akt, retinoblastoma protein (pRB) and ERK activity, with a concurrent loss of Akt expression. Inhibition of Akt and ERK activity induces apoptosis in other human cancer cell lines. Here it is demonstrated that inhibition of Akt, or ERK and Akt in combination, leads to cell cycle arrest but not apoptosis in melanoma cells. FTS treatment was also found to upregulate activity of the stress\u2010activated p38 MAP kinase. Inhibition of p38 MAP kinase, using the selective inhibitor SB 203580, followed by FTS treatment, significantly increased the proportion of apoptotic cells after 72 hr, possibly suggesting a modulatory role for p38 MAP kinase in FTS\u2010induced melanoma cell apoptosis. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.10213","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T23:09:26Z","timestamp":1030316966000},"page":"514-522","source":"Crossref","is-referenced-by-count":40,"title":["Farnesyl thiosalicylic acid inhibits the growth of melanoma cells through a combination of cytostatic and pro\u2010apoptotic effects"],"prefix":"10.1002","volume":"98","author":[{"given":"Keiran S.M.","family":"Smalley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim 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