Effects of teleocidin and the phorbol ester tumor promoters on cell transformation, differentiation, and phospholipid metabolism

Abstract

The potent tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) and related diterpene phorbol esters have been shown to enhance viral transformation and anchorage-independent growth, inhibit differentiation, and stimulate phosphatidylcholine turnover in various cell culture systems. In the present study, we report that teleocidin, and indole alkaloid isolated from Streptomyces, induces several biological effects similar to those of TPA in cell culture. Both TPA and teleocidin enhanced transformation of a clone of Fischer rat embryo cells (CREF) by a temperature-sensitive mutant of adenovirus type 5 (H5ts125); enhanced the cloning efficiency in agar of E11 cells, a clone of H5ts125-transformed Sprague-Dawley rat embryo cells; inhibited melanogenesis in murine B-16 melanoma cells; inhibited myogenesis in myoblast cultures established from normal human skeletal muscle; and stimulated choline release from prelabeled phospholipids of C3H10T 1/2 mouse cells. In general, TPA and teleocidin were equipotent in inducing these biological effects and were most active in the 3- to 10-ng/ml range, i.e., approximately 10(-8) to 10(-9) M. These studies provide further evidence that teleocidin represents a new class of tumor-promoting agents with properties similar to, if not identical with, those of the phorbol ester tumor promoters. These findings also suggest that cell culture systems can be used to identify new types of tumor-promoting agents in addition to the diterpene phorbol esters.