Inhibition of PKCalpha decreases the gelatinase activity and the angiogenic and metastatic ability of the highly metastatic B16 murine melanoma cells.

Protein kinase C (PKC) comprises a family of at least 11 isoforms that play a pivotal role in the angiogenic and metastatic process. In this study we analysed the effect of two PKC isoform-selective inhibitors, Gö6976 an inhibitor of c-PKCalpha and betaI, and bisindolylmaleimide (BIM) that prevents the effect of phorbol ester, on the gelatinolytic, angiogenic and metastatic capacity of the low metastatic B16F1 and the highly metastatic BL6 murine melanoma cells. The treatment with BIM did not modify these processes in either cell line, while Gö6976 induced a significant decrease in the angiogenic, gelatinase and metastatic potential in the BL6 cells. Both inhibitors inversely modulated VEGF and bFGF expression. Nitric oxide synthase (NOS), however, showed no change in activity. Taken together our results demonstrate an involvement of the c-PKCalpha isoform in the metastatic and angiogenic process, possibly by reducing the gelatinolytic activity. Thus, the c-PKCalpha isoform may be a novel target for therapy.