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

Abstract

Unlike initiating carcinogens, which seem to act by binding covalently to cellular DNA, the primary site of action of the phorbol esters seems to be the cell membrane; specific high-affinity saturable receptors for phorbol esters have in fact been identified in cell membranes. The teleocidins are as potent as TPA [12-O-tetradecanoylphorbol-13-acetate] in the induction of ornithine decarboxylase in mouse skin, the inhibition of differentiation of [mouse] Friend erythroleukemia cells, the induction of HL-60 cell adhesion and the promotion of tumors on mouse skin. Their effects on cell membranes and receptors were studied. In rodent cell cultures, teleocidin B and dihydroteleocidin B have effects similar to those of TPA and, at nanomolar concentrations, teleocidin inhibits the binding of phorbol esters to cell-surface receptors. The action of both classes of compounds may be mediated by the same or a similar receptor system.