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Farnesyl thiosalicylic acid inhibits the growth of melanoma cells through a combination of cytostatic and pro-apoptotic effects

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Date
2002-04-01
ICR Author
Eisen, Tim
Author
Smalley, KSM
Eisen, TG
Type
Journal Article
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Abstract
Novel classes of drug that interfere with the signalling of the small G-protein Ras, the so-called Ras antagonists, are showing much promise as novel anti-cancer agents. 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-apoptotic 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-dependent 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-activated 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-induced melanoma cell apoptosis. (C) 2002 Wiley-Liss, Inc.
URI
https://repository.icr.ac.uk/handle/internal/2796
DOI
https://doi.org/10.1002/ijc.10213
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Language
eng
License start date
2002-04-01
Citation
INTERNATIONAL JOURNAL OF CANCER, 2002, 98 pp. 514 - 522

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