Distinct Inhibitory Effects of Dihydroteleocidin B and the Phorbol Ester Tumor Promoters on the Adipocyte Differentiation of 3T3-L1 Cells¹

An indole alkaloid tumor promoter, dihydroteleocidin B, was able to modulate a membrane property of 3T3-L1 preadipocytes, showing an almost complete reduction of epidermal growth factor binding capacity. This receptor modulating potency of dihydroteleocidin B, was 10 times that of a phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Dihydroteleocidin B, however, had little effect on the epidermal growth factor receptors of the adipocyte stage of 3T3-L1. Adipocyte differentiation was induced by treating growth-arrested 3T3-L1 cells with dexamethasone and 1-methyl-3-isobutylxanthine for 48 hr. These inducers initiated DNA synthesis, led to one full cycle of cell division, and triggered the adipocyte differentiation program. Dihydroteleocidin B almost completely inhibited this differentiation at concentrations of 1 to 10 ng/ml (10^-9 to 10^-8 m). The inhibition was observed regardless of when the tumor promoter was added: before, during, or after the addition of inducers. Similar inhibition was also observed by TPA, but with over 90% less efficiency than that of dihydroteleocidin B. TPA was most effective when it was added during the inducer treatment. Both dihydroteleocidin B and TPA stimulated DNA synthesis to the same level during the initial 22 hr. The DNA synthesis stimulated by dihydroteleocidin B resulted in extraordinary enhancement of cell proliferation, whereas TPA-treated 3T3-L1 cells did not divide. These findings suggest that dihydroteleocidin B and TPA have distinct potencies in interfering with the mechanisms of adipocyte differentiation and that presumably they are different in action of tumorigenesis.