Similarity of teleocidin B and phorbol ester tumour promoters in effects on membrane receptors

Abstract

The tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and structurally related phorbol esters effect changes in avian and mammalian cell cultures that mimic transformation by oncogenic viruses or chemical carcinogens and the inhibition or induction of various types of differentiation (for review see refs 1–3). Unlike initiating carcinogens, which seem to act by binding covalently to cellular DNA, the primary site of action of the phorbol ester tumour promoters seems to be the cell membrane^2,3; indeed, specific high-affinity saturable receptors for phorbol esters have been identified in cell membranes^4,5. The recently discovered class of tumour promoters, the teleocidins⁶, are as potent as TPA in the induction of ornithine decarboxylase in mouse skin, the inhibition of differentiation of Friend eryth-roleukaemia cells, the induction of HL-60 cell adhesion⁶ and the promotion of tumours on mouse skin⁷. As the teleocidins are structurally unrelated to the phorbol esters, weset out to determine their effects on cell membranes and receptors. We found that in rodent cell cultures, teleocidin B and dihydroteleocidin B have effects similar to those of TPA and that, at nanomolar concentrations, teleocidin inhibits the binding of phorbol esters to cell-surface receptors, which suggests that the action of both classes of compounds may be mediated by the same or a similar receptor system.