1,2-Dioctanoyl-glycerol induces a discrete but transient translocation of protein kinase C as well as the inhibition of MCF-7 cell proliferation

Abstract Exposure of MCF-7 human breast cancer cells to phorbol esters such as 12-O-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 (diC 8 ) on both protein kinase C activity and MCF-7 cell proliferation. DiC 8 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 μg/ml diC 8 ). However, this effect is only transient as the enzymatic activity returns to the control value after 60 min. DiC 8 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 diC 8 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 diC 8 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 prerequisite in the biological cell response.