The novel Ras antagonist, farnesylthiosalicylate, suppresses growth of prostate cancer in vitro.

BACKGROUND

The majority of men with advanced prostate cancer (PCa) respond to androgen deprivation therapy (ADT) with objective evidence of tumor regression. However, these tumors will regrow in the presence of low-androgen levels after 12-18 months. Regrowth after ADT is associated with upregulation of growth factor (GF) mediated pathways. The compound farnesylthiosalicylate (FTS), a specific antagonist of the 21 kDa Ras protein, suppresses GF signaling and it might be a useful therapy against advanced PCa.

METHODS

We measured androgen and GF dependent growth of androgen dependent LNCaP and androgen hypersensitive CWR-R1 PCa cells in response to specific inhibitors of GF pathways, including FTS. Inhibition of GF mediated signaling and cell-cycle pathways was confirmed by Western blotting of extracts from treated cells.

RESULTS

Both LNCaP and CWR-R1 cells were dependent on GF signaling pathways for cell growth. FTS, as well as suppressing cell growth, inhibited GF signaling pathway activity and reduced the levels of E2F1, p-Rb, and p-cdc2, all GF dependent mediators of cell-cycle progression.

CONCLUSIONS

These data suggest that FTS might be a useful agent against PCa that has relapsed after ADT.