ANALOGS OF FARNESYLCYSTEINE INDUCE APOPTOSIS IN HL-60 CELLS

S-Farnesyl-thioacetic acid (FTA), a competitive inhibitor of isoprenyl ated protein methyltransferase, potently suppressed the growth of HL-6 0 cells and induced apoptosis, as evidenced by the development of incr eased annexin-V binding, decreased binding of DNA dyes and internucleo somal DNA degradation. FTA did not impair the membrane association of ras proteins, conversely, it brought about a decrease in the proportio n of ras present in the cytosolic fraction, Farnesylated molecules whi ch are weak inhibitors of the methyltransferase also induced DNA ladde ring and reduced the proportion of cytosolic ras, Those findings sugge st that neither inhibition of isoprenylated protein methylation nor im pairment of ras membrane association are essential for apoptosis induc ed by farnesylcysteine analogs. (C) 1998 Federation of European Bioche mical Societies.