Interaction between phorbol esters and phospholipid in a monolayer model membrane.

The possible molecular interaction between phorbol esters and a phospholipid was examined in monolayer films at an air-water interface. The surface pressure isotherms indicated that, at close-to-physiological pressure, there existed a repulsive interaction between the phospholipid and biologically active phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and phorbol 12,13-didecanoate (PDD). There was a close parallelism between the relative biological potency of different phorbol esters, as tumour promoters, and the magnitude of their repulsive interaction with the phospholipid. These findings raise the possibility that a biophysical interference of phorbol esters with the phospholipid domain of biological membranes may represent an important determinant of their biological actions.