Selective farnesol toxicity and translocation of protein kinase C in neoplastic HeLa-S3K and non-neoplastic CF-3 cells.
We have reported earlier that farnesol, a 15 carbon isoprenoid, has inhibitory effects on the growth and viability of a variety of cultured cells of neoplastic derivation but is considerably less cytotoxic to cells derived from normal tissue (Cancer Lett., 79, 175-179). As part of our search for the mechanism of this observation, we have studied the effect of 20 microM farnesol on the distribution of protein kinase C (PKC) between cytosolic and membrane fractions of HeLa S3K cells and fibroblasts line CF-3. In HeLa cells farnesol caused translocation of PKC from membrane fraction to cytosol after 1h of incubation and also prevented PMA-stimulated induction of PKC translocation from cytosol to membranes. Up to 6 h of incubation, there was no effect of farnesol on PKC localization in CF-3 fibroblasts. The results point to possible involvement of PKC in the toxic effect of farnesol which occurs with some degree of selectivity depending on cell origin.
Yazlovitskaya
E M
EM
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City 66103.
Melnykovych
G
G
D002462:Cell Membrane / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000201:enzymology; D005204:Farnesol / Q000633:toxicity*; D005347:Fibroblasts / Q000201:enzymology; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology
D009363:Neoplasm Proteins; D005204:Farnesol; D011493:Protein Kinase C