1,2-Dioctanoyl-glycerol induces a discrete but transient translocation of protein kinase C as well as the inhibition of MCF-7 cell proliferation.
Exposure of MCF-7 human breast cancer cells to phorbol esters such as 12-0-tetradecanoylphorbol-13-acetate (TPA) results in a dose-dependent inhibition of cell proliferation. One of the earliest biochemical events induced by TPA is the translocation of protein kinase C from the cytosolic to the particulate compartment. We have investigated the effects of permeant diacylglycerol 1,2-dioctanoyl-glycerol (diC8) on both protein kinase C activity and MCF-7 cell proliferation. DiC8 induces a discrete but significant translocation of protein kinase C within the first minutes of MCF-7 cell treatment (26 +/- 6%, mean +/- SD of 5 different experiments, upon 5 min incubation in the presence of 43 micrograms/ml diC8). However, this effect is only transient as the enzymatic activity returns to the control value after 60 min. DiC8 mimics the effect of TPA on MCF-7 cell proliferation. The dose-response curves for both protein kinase C translocation and cell growth inhibition show that diC8 exerts its effects on both parameters in the same range of concentrations, despite some discrepancies at the lowest doses. We also report that long-term treatment of the cells with diC8 does not lead to the protein kinase C disappearance observed during prolonged exposure to TPA. All together, our results reinforce the hypothesis of a negative modulatory role of protein kinase C in MCF-7 cell proliferation and suggest that the enzyme translocation but not its down-regulation could be a pre-requisite in the biological cell response.
Issandou
M
M
INSERM U 168, Department of Endocrinology, CHU Rangueil Université Paul Sabatier, Toulouse, France.
Darbon
J M
JM
D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects*; D003600:Cytosol / Q000201:enzymology; D004075:Diglycerides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004075:Diglycerides; D005989:Glycerides; C044295:1,2-dioctanoylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate