Protein kinase C epsilon mediates the induction of P-glycoprotein in LNCaP prostate carcinoma cells.

P-glycoprotein (P-gp) mediates drug resistance. Protein kinase C (PKC) expression correlates with drug resistance in several types of cancer. We determined whether PKC signals the induction of P-gp in LNCaP human prostate cancer cells, and identified a specific isozyme involved, in a model of aspirin-induced P-glycoprotein expression. An inhibitor of PKC activity, and a specific peptide inhibitor of PKC epsilon translocation, suppressed the induction of P-gp. The PKC activator ingenol, but not OAG, induced P-gp expression in a dose-dependent manner. Based on our results, we conclude that PKC epsilon mediates the induction of P-gp. Accordingly, PKC epsilon is activated and translocates from the membrane fraction to the cytoskeleton fraction in aspirin-treated cells. The findings of this study point to PKC epsilon as a signalling molecule for the induction of P-gp in LNCaP prostate cancer cells.