Bryostatins: potent, new mitogens that mimic phorbol ester tumor promoters

Bryostatins (2 ng/ml), when combined with insulin in serum-free culture medium, are strongly mitogenic for Swiss 3T3 cells that have been arrested in the G1/G0 phase of the cell cycle. The mitogenic effect of the bryostatins is similar to that of 12-O-decanoylphorbol-13-acetate (TPA). A prior treatment of the cultures with TPA eliminated the mitogenic response to bryostatin and to a second addition of TPA. Conversely, a prior treatment of the cultures with bryostatin eliminated the mitogenic response to TPA. Bryostatin potently inhibited the binding of [3H]phorbol dibutyrate to a high affinity receptor in the cells. The findings suggest that the bryostatins and TPA act via the same receptor, possibly protein kinase C.