Analogs of farnesylcysteine induce apoptosis in HL-60 cells

S-Farnesyl-thioacetic acid (FTA), a competitive inhibitor of isoprenylated protein methyltransferase, potently suppressed the growth of HL-60 cells and induced Apoptosis, as evidenced by the development of increased annexin-V binding, decreased binding of DNA dyes and internucleosomal DNA degradation. FTA did not impair the membrane association of Ras proteins, conversely, it brought about a decrease in the proportion of Ras present in the cytosolic fraction. Farnesylated molecules which are weak inhibitors of the methyltransferase also induced DNA laddering and reduced the proportion of cytosolic Ras. These findings suggest that neither inhibition of isoprenylated protein methylation nor impairment of Ras membrane association are essential for Apoptosis induced by farnesylcysteine analogs.