PMID: 11920610Mar 29, 2002Paper

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

International Journal of Cancer. Journal International Du Cancer
K S M Smalley, Tim G Eisen

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.

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Citations

Apr 16, 2013·Cancer Metastasis Reviews·Yabin ChengGang Li
Jun 5, 2012·Genes & Development·Hensin TsaoDavid E Fisher
Oct 4, 2011·Trends in Molecular Medicine·Zhenyu JiHensin Tsao
Jan 26, 2010·European Journal of Pharmacology·Chung Soo LeeWonyong Kim
Jan 22, 2003·The Journal of Investigative Dermatology·Julius Halaschek-WienerBurkhard Jansen
Oct 31, 2007·Free Radical Biology & Medicine·Kazi Mokim Ahmed, Jian Jian Li
Feb 21, 2003·International Journal of Cancer. Journal International Du Cancer·Keiran S M Smalley
Jun 16, 2005·International Journal of Cancer. Journal International Du Cancer·Wei YueRichard J Santen
Dec 10, 2009·International Journal of Cancer. Journal International Du Cancer·Shira Yaari-StarkYoel Kloog
Nov 19, 2004·Journal of the American Society of Nephrology : JASN·Julie M Williams, Caroline O S Savage
Oct 22, 2005·Cell Death and Differentiation·S AmosI M Hussaini
Apr 4, 2003·International Journal of Cancer. Journal International Du Cancer·Keiran S M Smalley, Tim G Eisen
Jan 22, 2019·Frontiers in Pharmacology·Huanbiao MoHoda Yeganehjoo

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