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.
Pérez-Sala
D
D
Departamento de Estructura y Función de Proteínas, Centro de Investigaciones Biológicas, C.S.I.C., Madrid, Spain. lperezsala@fresno.csic.es
Gilbert
B A
BA
Rando
R R
RR
Cañada
F J
FJ
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects; D005204:Farnesol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D011506:Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D018631:ras Proteins / Q000187:drug effects / Q000378:metabolism
D006131:Growth Inhibitors; D011506:Proteins; C112353:farnesylthioacetic acid; D005204:Farnesol; C057785:S-farnesylcysteine; D018631:ras Proteins; D003545:Cysteine; C068268:N-acetyl-S-farnesylcysteine; D000111:Acetylcysteine