title: Distinct inhibitory effects of dihydroteleocidin B and the phorbol ester tumor promoters on the adipocyte differentiation of 3T3-L1 cells.
abstract: 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.
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D008235:Lyngbya Toxins; D051379:Mice; D010704:Phorbols / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000470:Alkaloids; D002273:Carcinogens; D008235:Lyngbya Toxins; D010704:Phorbols; D003907:Dexamethasone; C022229:dihydroteleocidin B; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine